Tricyclic taxanes having an alkoxy, alkenoxy or aryloxy substituted side-chain and pharmaceutical compositions containing them

ABSTRACT

Taxane derivatives having an alkoxy, alkenoxy or aryloxy substituted C13 side chain.

This invention was made with Government support under NIH Grant #CA42031 and NIH Grant #CA 55131 awarded by the National Institutes ofHealth. The Government has certain rights in the invention.

REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. Ser. No.08/461,103, filed Jun. 5, 1995 now U.S. Pat. No. 5,739,362, which is afile wrapper continuation application of U.S. Ser. No. 08/094,717 filedJul. 20, 1993 now abandoned, which is a continuation-in-part ofapplication of U.S. Ser. No. 08/034,247, filed Mar. 22, 1993, now U.S.Pat. No. 5,430,160, which is a continuation-in-part application of U.S.Ser. No. 07/949,107, filed Sep. 22, 1992 now abandoned, which is acontinuation-in-part application of U.S. Ser. No. 07/863,849, filed Apr.6, 1992, now abandoned, which is a continuation-in-part application ofU.S. Ser. No. 07/862,955, filed Apr. 3, 1992, now abandoned, which is acontinuation-in-part of U.S. Ser. No. 07/763,805, filed Sep. 23, 1991,now abandoned. This application is also a continuation-in-partapplication of U.S. Ser. No. 08/034,852, filed Mar. 22, 1993, nowabandoned. This application is also a continuation-in-part applicationof U.S. Ser. No. 07/863,198, filed Apr. 3, 1992, now U.S. Pat. No.5,243,045.

BACKGROUND OF THE INVENTION

The present invention is directed to novel taxanes which have utility asantileukemia and antitumor agents.

The taxane family of terpenes, of which taxol is a member, has attractedconsiderable interest in both the biological and chemical arts. Taxol isa promising cancer chemotherapeutic agent with a broad spectrum ofantileukemic and tumor-inhibiting activity. Taxol has a 2'R, 3'Sconfiguration and the following structural formula: ##STR1## wherein Acis acetyl. Because of this promising activity, taxol is currentlyundergoing clinical trials in both France and the United States.

Colin et al. reported in U.S. Pat. No. 4,814,470 that taxol derivativeshaving structural formula (2) below, have an activity significantlygreater than that of taxol (1) . ##STR2## R' represents hydrogen oracetyl and one of R" and R"' represents hydroxy and the other representstert-butoxy-carbonylamino and their stereoisomeric forms, and mixturesthereof. The compound of formula (2) in which R' is hydrogen R" ishydroxy, R"' is tert-butoxycarbonylamino having the 2'R, 3'Sconfiguration is commonly referred to as taxotere.

Although taxol and taxotere are promising chemotherapeutic agents, theyare not universally effective. Accordingly, a need remains foradditional chemotherapeutic agents.

SUMMARY OF THE INVENTION

Among the objects of the present invention, therefore, is the provisionof novel taxane derivatives which are valuable antileukemia andantitumor agents.

Briefly, therefore, the present invention is directed to taxanederivatives having a C13 side chain which includes an alkoxy or alkenoxysubstituent, but which differs from taxotere with respect to at leastone substituent. In a preferred embodiment, the taxane derivative has atricyclic or tetracyclic core and corresponds to the formula: ##STR3##wherein X₁ is --OX₆, --SX₇, or --NX₈ X₉ ;

X₂ is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;

X₃ and X₄ are independently hydrogen, alkyl, alkenyl, alkynyl, aryl orheteroaryl;

X₅ is --COOX₁₀ ;

X₆ is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, hydroxyprotecting group, or a functional group which increases the watersolubility of the taxane derivative;

X₇ is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or sulfhydrylprotecting group;

X₈ is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, orheterosubstituted alkyl, alkenyl, alkynyl, aryl or heteroaryl;

X₉ is an amino protecting group;

X₁₀ is alkyl, alkenyl or aryl;

R₁ is hydrogen, hydroxy, protected hydroxy, or together with R₁₄ forms acarbonate;

R₂ is hydrogen, hydroxy, --OCOR₃₁ or together with R_(2a) forms an oxo;

R_(2a) is hydrogen or taken together with R₂ forms an oxo;

R₄ is hydrogen, together with R_(4a) forms an oxo, oxirane or methylene,or together with R_(5a) and the carbon atoms to which they are attachedform an oxetane ring;

R_(4a) is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyano,hydroxy, --OCOR₃₀, or together with R₄ forms an oxo, oxirane ormethylene;

R₅ is hydrogen or together with R_(5a) forms an oxo,

R_(5a) is hydrogen, hydroxy, protected hydroxy, acyloxy, together withR₅ forms an oxo, or together with R₄ and the carbon atoms to which theyare attached form an oxetane ring;

R₆ is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy,protected hydroxy or together with R_(6a) forms an oxo;

R_(6a) is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl,hydroxy, protected hydroxy or together with R₆ forms an oxo;

R₇ is hydrogen or together with R_(7a) forms an oxo,

R_(7a) is hydrogen, halogen, protected hydroxy, --OR₂₈, or together withR₇ forms an oxo;

R₉ is hydrogen or together with R_(9a) forms an oxo,

R_(9a) is hydrogen, hydroxy, protected hydroxy, acyloxy, or togetherwith R₉ forms an oxo;

R₁₀ is hydrogen or together with R_(10a) forms an oxo,

R_(10a) is hydrogen, --OCOR₂₉, hydroxy, or protected hydroxy, ortogether with R₁₀ forms an oxo;

R₁₄ is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy,protected hydroxy or together with R₁ forms a carbonate;

R_(14a) is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;

R₂₈ is hydrogen, acyl, hydroxy protecting group or a functional groupwhich increases the solubility of the taxane derivative;

R₂₉, R₃₀, and R₃₁ are independently hydrogen, alkyl, alkenyl, alkynyl,monocyclic aryl or monocyclic heteroaryl, provided, however, that whenX₁₀ is t-butyl at least one of said other X₁ -X₉ or R₁ -R₃₁ has a valuesuch that the structure of the taxane is different from that oftaxotere.

Other objects and features of this invention will be in part apparentand in part pointed out hereinafter.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As used herein "Ar" means aryl; "Ph" means phenyl; "Ac" means acetyl;"Et" means ethyl; "R" means alkyl unless otherwise defined; "Bu" meansbutyl; "Pr" means propyl; "TES" means triethylsilyl; "TMS" meanstrimethylsilyl; "TPAP" means tetrapropylammonium perruthenate; "DMAP"means p-dimethylamino pyridine; "DMF" means dimethylformamide; "LDA"means lithium diisopropylamide; "LHMDS" means lithiumhexamethyldisilazide; "LAH" means lithium aluminum hydride; "Red-Al"means sodium bis(2-methoxyethoxy)aluminum hydride; "AIBN" meansazo-(bis)-isobutyronitrile; "10-DAB" means 10-desacetylbaccatin III; FARmeans 2-chloro-1,1,2-trifluorotriethylamine; protected hydroxy means--OR wherein R is a hydroxy protecting group; sulfhydryl protectinggroup" includes, but is not limited to, hemithioacetals such as1-ethoxyethyl and methoxymethyl, thioesters, or thiocarbonates; "amineprotecting group" includes, but is not limited to, carbamates, forexample, 2,2,2-trichloroethylcarbamate or tertbutylcarbamate; and"hydroxy protecting group" includes, but is not limited to, ethers suchas methyl, t-butyl, benzyl, p-methoxybenzyl, p-nitrobenzyl, allyl,trityl, methoxymethyl, 2-methoxypropyl, methoxyethoxymethyl,ethoxyethyl, tetrahydropyranyl, tetrahydrothiopyranyl, and trialkylsilylethers such as trimethylsilyl ether, triethylsilyl ether,dimethylarylsilyl ether, triisopropylsilyl ether andt-butyldimethylsilyl ether; esters such as benzoyl, acetyl,phenylacetyl, formyl, mono-, di-, and trihaloacetyl such aschloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl; andcarbonates including but not limited to alkyl carbonates having from oneto six carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl,t-butyl; isobutyl, and n-pentyl; alkyl carbonates having from one to sixcarbon atoms and substituted with one or more halogen atoms such as2,2,2-trichloroethoxymethyl and 2,2,2-trichloro-ethyl; alkenylcarbonates having from two to six carbon atoms such as vinyl and allyl;cycloalkyl carbonates having from three to six carbon atoms such ascyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; and phenyl orbenzyl carbonates optionally substituted on the ring with one or moreC₁₋₆ alkoxy, or nitro. Other hydroxyl, sulfhydryl and amine protectinggroups may be found in "Protective Groups in Organic Synthesis" by T. W.Greene, John Wiley and Sons, 1981.

The alkyl groups described herein, either alone or with the varioussubstituents defined herein are preferably lower alkyl containing fromone to six carbon atoms in the principal chain and up to 15 carbonatoms. They may be substituted, straight, branched chain or cyclic andinclude methyl, ethyl, propyl, isopropyl, butyl, hexyl, cyclopropyl,cyclopentyl, cyclohexyl and the like.

The alkenyl groups described herein, either alone or with the varioussubstituents defined herein are preferably lower alkenyl containing fromtwo to six carbon atoms in the principal chain and up to 15 carbonatoms. They may be substituted, straight or branched chain and includeethenyl, propenyl, isopropenyl, butenyl, isobutenyl, hexenyl, and thelike.

The alkynyl groups described herein, either alone or with the varioussubstituents defined herein are preferably lower alkynyl containing fromtwo to six carbon atoms in the principal chain and up to 15 carbonatoms. They may be substituted, straight or branched chain and includeethynyl, propynyl, butynyl, isobutynyl, hexynyl, and the like.

The aryl moieties described herein, either alone or with varioussubstituents, contain from 6 to 15 carbon atoms and include phenyl.Substituents include alkanoxy, protected hydroxy, halogen, alkyl, aryl,alkenyl, acyl, acyloxy, nitro, amino, amido, etc. Phenyl is the morepreferred aryl.

The heteroaryl moieties described herein, either alone or with varioussubstituents, contain from 5 to 15 atoms and include, furyl, thienyl,pyridyl and the like. Substituents include alkanoxy, protected hydroxy,halogen, alkyl, aryl, alkenyl, acyl, acyloxy, nitro, amino, and amido.

The acyloxy groups described herein contain alkyl, alkenyl, alkynyl,aryl or heteroaryl groups.

The substituents of the substituted alkyl, alkenyl, alkynyl, aryl, andheteroaryl groups and moieties described herein, may be alkyl, alkenyl,alkynyl, aryl, heteroaryl and/or may contain nitrogen, oxygen, sulfur,halogens and include, for example, lower alkoxy such as methoxy, ethoxy,butoxy, halogen such as chloro or fluoro, nitro, amino, and keto.

In accordance with the present invention, it has been discovered thatcompounds corresponding to structural formula 3 show remarkableproperties, in vitro, and are valuable antileukemia and antitumoragents. Their biological activity has been determined in vitro, usingtubulin assays according to the method of Parness et al., J. CellBiology, 91: 479-487 (1981) and human cancer cell lines, and iscomparable to that exhibited by taxol and taxotere.

In one embodiment of the present invention, the substituents of thecyclic nucleus of the taxane (other than the C13 substituent) correspondto the substituents present on baccatin III or 10-DAB. That is, R₁₄ andR_(14a) are hydrogen, R₁₀ is hydrogen, R_(10a) is hydroxy or acetoxy, R₉and R_(9a) together form an oxo, R₇ is hydrogen, R_(7a) is hydroxy, R₅is hydrogen, R_(5a) and R₄ and the carbons to which they are attachedform an oxetane ring, R_(4a) is acetoxy, R₂ is hydrogen, R_(2a) isbenzoyloxy, and R₁₄ is hydroxy. In other embodiments, the taxane has astructure which differs from that of taxol or taxotere with respect tothe C13 side chain and at least one other substituent. For example, R₁may be hydroxy, R₂ may be hydroxy or --OCOR₃₁ wherein R₃₁ is hydrogen,alkyl or selected from the group comprising ##STR4## and Z is alkyl,hydroxy, alkoxy, halogen, or trifluoromethyl. R_(9a) may be hydrogen andR₉ may be hydrogen or hydroxy, R_(7a) may be hydrogen and R₇ may beacetoxy or other acyloxy or halogen, or R₁₀ and R_(10a) may each behydrogen or together form an oxo.

With respect to the C13 side-chain, in a preferred embodiment X₁ is--OH, X₂ is hydrogen, X₃ is alkyl, alkenyl, phenyl or heteroaryl, X₄ ishydrogen, X₅ is --COOX₁₀, and X₁₀ is C3 to C8 alkyl, alkenyl or aryl andthe taxane has the 2'R, 3'S configuration. In a particularly preferredembodiment, X₃ is phenyl, isopropyl, cyclopropyl, n-butyl, t-butyl,n-butyl, t-butyl, cyclobutyl, cyclohexyl, furyl, thienyl, pyridyl or thesubstituted analogs thereof, X₅ is --COOX₁₀ and X₁₀ is methyl, ethyl,cyclopropyl, iso- or n-propyl, cyclohexyl, allyl, crotyl,1,3-diethoxy-2-propyl, 2-methoxy-ethyl, amyl, neopentyl, n-butyl,iso-butyl or tert-butyl.

Significantly, however, when X₅ is tert-butyl at least one of X₁ -X₉ andR₁ -R₃₁ has a value such that the structure of the taxane is differentfrom that of taxotere. For example, when X₅ is t-butyl at least one ofthe following conditions shall exist:

X₁ is --OX₆, --SX₇, or --NX₈ X₉ and X₆ is other than hydrogen or hydroxyprotecting group;

X₂ is other than hydrogen;

at least one of X₃ and X₄ shall be other than hydrogen and phenyl;

R₁ is hydroxy or together with R₁₄ forms a carbonate;

R₂ is other than benzoyloxy;

R₄ and R_(5a) and the carbon atoms to which they are attached do notform an oxetane ring;

R_(4a) is other than acetoxy;

R₆ and R_(6a) are other than hydrogen;

R_(7a) is other than hydroxy;

R₉ and R_(9a) together do not form an oxo;

R_(10a) is other than hydroxy; or

R₁₄ and R_(14a) are other than hydrogen.

Taxanes having the general formula 3 may be obtained by reacting aβ-lactam with alkoxides having the taxane tricyclic or tetracyclicnucleus and a C-13 metallic oxide substituent to form compounds having aβ-amido ester substituent at C-13. The β-lactams have the followingstructural formula: ##STR5## wherein X₁ -X₅ are as defined above.

The β-lactams can be prepared from readily available materials, as isillustrated in schemes A and B below: ##STR6## reagents: (a)triethylamine, CH₂ Cl₂, 25° C., 18 h; (b) 4 equiv ceric ammoniumnitrate, CH₃ CN, -10° C., 10 min; (c) KOH, THF, H₂ O, 0° C., 30 min, orpyrolidine, pyridine, 25° C., 3 h, (d) TESCl, pyridine, 25° C., 30 minor 2-methoxypropene toluene sulfonic acid (cat.), THF, 0° C., 2 h; (e)n-butyllithium, THF, -78° C., 30 min; and an acyl cloride orchloroformate (X₅ =--COX₁₀), sulfonyl chloride (X₅ =--COSX₁₀) orisocyanate (X₅ =--CONX₈ X₁₀); (f) lithium diisopropyl amide, THF -78° C.to -50° C.; (g) lithium hexamethyldisilazide, THF -78° C. to 0° C.; (h)THF, -78° C. to 25° C., 12 h.

The starting materials are readily available. In scheme A, α-acetoxyacetyl chloride is prepared from glycolic acid, and, in the presence ofa tertiary amine, it cyclocondenses with imines prepared from aldehydesand p-methoxyaniline to give1-p-methoxyphenyl-3-acyloxy-4-arylazetidin-2-ones. The p-methoxyphenylgroup can be readily removed through oxidation with ceric ammoniumnitrate, and the acyloxy group can be hydrolyzed under standardconditions familiar to those experienced in the art to provide3-hydroxy-4-arylazetidin-2-ones. In Scheme B,ethyl-α-triethylsilyloxyacetate is readily prepared from glycolic acid.

In Schemes A and B, X, is preferably --OX₆ and X₆ is a hydroxyprotecting group. Protecting groups such as 2-methoxypropyl ("MOP"),1-ethoxyethyl ("EE") are preferred, but a variety of other standardprotecting groups such as the triethylsilyl group or other trialkyl (oraryl) silyl groups may be used. As noted above, additional hydroxyprotecting groups and the synthesis thereof may be found in "Protectivegroups in Organic Synthesis" by T. W. Greene, John Wiley & Sons, 1981.

The racemic β-lactams may be resolved into the pure enantiomers prior toprotection by recrystallization of the corresponding2-methoxy-2-(trifluoromethyl)phenylacetic esters. However, the reactiondescribed hereinbelow in which the β-amido ester side chain is attachedhas the advantage of being highly diastereoselective, thus permittingthe use of a racemic mixture of side chain precursor.

The alkoxides having the tricyclic or tetracyclic taxane nucleus and aC-13 metallic oxide or ammonium oxide substituent have the followingstructural formula: ##STR7## wherein R₁ -R_(14a) are as previouslydefined and M comprises ammonium or is a metal optionally selected fromthe group comprising Group IA, Group IIA and transition metals, andpreferably, Li, Mg, Na, K or Ti. Most preferably, the alkoxide has thetetracyclic taxane nucleus and corresponds to the structural formula:##STR8## wherein M, R₂, R_(4a), R₇, R_(7a), R₉, R_(9a), R₁₀, and R_(10a)are as previously defined.

The alkoxides can be prepared by reacting an alcohol having the taxanenucleus and a C-13 hydroxyl group with an organometallic compound in asuitable solvent. Most preferably, the alcohol is a protected baccatinIII, in particular, 7-O-triethylsilyl baccatin III (which can beobtained as described by Greene, et al. in JACS 110: 5917 (1988) or byother routes) or 7,10-bis-O-triethylsilyl baccatin III.

As reported in Greene et al., 10-deacetyl baccatin III is converted to7-O-triethylsilyl-10-deacetyl baccatin III according to the followingreaction scheme: ##STR9## Under what is reported to be carefullyoptimized conditions, 10-deacetyl baccatin III is reacted with 20equivalents of (C₂ H₅)₃ SiCl at 23° C. under an argon atmosphere for 20hours in the presence of 50 ml of pyridine/mmol of 10-deacetyl baccatinIII to provide 7-triethylsilyl-10-deacetyl baccatin III (4a) as areaction product in 84-86% yield after purification. The reactionproduct may then optionally be acetylated with 5 equivalents of CH₃ COCland 25 mL of pyridine/mmol of 4a at 0° C. under an argon atmosphere for48 hours to provide 86% yield of 7-O-triethylsilyl baccatin III (4b).Greene, et al. in JACS 110, 5917 at 5918 (1988).

The 7-protected baccatin III (4b) is reacted with an organometalliccompound such as LHMDS in a solvent such as tetrahydrofuran (THF), toform the metal alkoxide 13-O-lithium-7-O-triethylsilyl baccatin III asshown in the following reaction scheme: ##STR10##

As shown in the following reaction scheme,13-O-lithium-7-O-triethylsilyl baccatin III reacts with a β-lactam inwhich X₁ is preferably --OX₆, (X₆ being a hydroxy protecting group) andX₂ -X₅ are as previously defined to provide an intermediate in which theC-7 and C-2' hydroxyl groups are protected. The protecting groups arethen hydrolyzed under mild conditions so as not to disturb the esterlinkage or the taxane substituents. ##STR11##

Both the conversion of the alcohol to the alkoxide and the ultimatesynthesis of the taxane derivative can take place in the same reactionvessel. Preferably, the β-lactam is added to the reaction vessel afterformation therein of the alkoxide.

Compounds of formula 3 of the instant invention are useful forinhibiting tumor growth in animals including humans and are preferablyadministered in the form of a pharmaceutical composition comprising aneffective antitumor amount of compound of the instant invention incombination with a pharmaceutically acceptable carrier or diluent.

Antitumor compositions herein may be made up in any suitable formappropriate for desired use; e.g., oral, parenteral or topicaladministration. Examples of parenteral administration are intramuscular,intravenous, intraperitoneal, rectal and subcutaneous administration.

The diluent or carrier ingredients should not be such as to diminish thetherapeutic effects of the antitumor compounds.

Suitable dosage forms for oral use include tablets, dispersible powders,granules, capsules, suspensions, syrups, and elixirs. Inert diluents andcarriers for tablets include, for example, calcium carbonate, sodiumcarbonate, lactose and talc. Tablets may also contain granulating anddisintegrating agents such as starch and alginic acid, binding agentssuch as starch, gelatin and acacia, and lubricating agents such asmagnesium stearate, stearic acid and talc. Tablets may be uncoated ormay be coated by unknown techniques; e.g., to delay disintegration andabsorption. Inert diluents and carriers which may be used in capsulesinclude, for example, calcium carbonate, calcium phosphate and kaolin.Suspensions, syrups and elixirs may contain conventional excipients, forexample, methyl cellulose, tragacanth, sodium alginate; wetting agents,such as lecithin and polyoxyethylene stearate; and preservatives, e.g.,ethyl-p-hydroxybenzoate.

Dosage forms suitable for parenteral administration include solutions,suspensions, dispersions, emulsions and the like. They may also bemanufactured in the form of sterile solid compositions which can bedissolved or suspended in sterile injectable medium immediately beforeuse. They may contain suspending or dispersing agents known in the art.

The water solubility of compounds of formula (3) may be improved bymodification of the C2' and/or C7 substituents. For instance, watersolubility may be increased if X₁ is --OX₆ and R_(7a) is --OR₂₈, and X₆and R₂₈ are independently hydrogen or --COGCOR¹ wherein

G is ethylene, propylene, --CH═CH--, 1,2-cyclohexane, or 1,2-phenylene,

R¹ =OH base, NR² R³, OR³, SR³, OCH₂ CONR⁴ R⁵, OH

R² =hydrogen, methyl

R³ =(CH₂)_(n) NR⁶ R⁷ ; (CH₂)_(n) N.sup.⊕ R⁶ R⁷ R⁸ X.sup.⊖

n=1 to 3

R⁴ =hydrogen, lower alkyl containing 1 to 4 carbons

R⁵ =hydrogen, lower alkyl containing 1 to 4 carbons, benzyl,hydroxyethyl, CH₂ CO₂ H, dimethylaminoethyl

R⁶ R⁷ =lower alkyl containing 1 or 2 carbons, benzyl or R⁶ and

R⁷ together with the nitrogen atom of NR⁶ R⁷ form the following rings##STR12## R⁸ =lower alkyl containing 1 or 2 carbons, benzyl X.sup.⊖=halide

base=NH₃, (HOC₂ H₄)₃ N, N(CH₃)₃, CH₃ N(C₂ H₄ OH)₂, NH₂ (CH₂)₆ NH₂,N-methylglucamine, NaOH, KOH.

The preparation of compounds in which X₁ or X₂ is --COGCOR¹ is set forthin Haugwitz U.S. Pat. No. 4,942,184 which is incorporated herein byreference.

Alternatively, solubility may be increased when X₁ is --OX₆ and X₆ is aradical having the formula --COCX═CHX or --COX--CHX--CHX--SO₂ O--Mwherein X is hydrogen, alkyl or aryl and M is hydrogen, alkaline metalor an ammonio group as described in Kingston et al., U.S. Pat. No.5,059,699 (incorporated herein by reference).

Taxanes having alternative C9 substituents may be prepared byselectively reducing the C9 keto substituent to yield the correspondingC9 β-hydroxy derivative. The reducing agent is preferably a borohydrideand, most preferably, tetrabutylammoniumborohydride (Bu₄ NBH₄) ortriacetoxyborohydride.

As illustrated in Reaction Scheme 1, the reaction of baccatin III withBu₄ NBH₄ in methylene chloride yields 9-desoxo-9β-hydroxybaccatin III 5.After the C7 hydroxy group is protected with the triethylsilylprotecting group, for example, a suitable side chain may be attached to7-protected-9β-hydroxy derivative 6 as elsewhere described herein.Removal of the remaining protecting groups thus yields 9β-hydroxy-desoxotaxol or other 9β-hydroxytetracylic taxane having a C13 side chain.##STR13##

Alternatively, the C13 hydroxy group of 7-protected-9β-hydroxyderivative 6 may be protected with trimethylsilyl or other protectinggroup which can be selectively removed relative to the C7 hydroxyprotecting group as illustrated in Reaction Scheme 2, to enable furtherselective manipulation of the various substituents of the taxane. Forexample, reaction of 7,13-protected-9β-hydroxy derivative 7 with KHcauses the acetate group to migrate from C10 to C9 and the hydroxy groupto migrate from C9 to C10, thereby yielding 10-desacetyl derivative 8.Protection of the C10 hydroxy group of 10-desacetyl derivative 8 withtriethylsilyl yields derivative 9. Selective removal of the C13 hydroxyprotecting group from derivative 9 yields derivative 10 to which asuitable side chain may be attached as described above. ##STR14##

As shown in Reaction Scheme 3, 10-oxo derivative 11 can be provided byoxidation of 10-desacetyl derivative 8. Thereafter, the C13 hydroxyprotecting group can be selectively removed followed by attachment of aside chain as described above to yield 9-acetoxy-10-oxo-taxol or other9-acetoxy-10-oxotetracylic taxanes having a C13 side chain.Alternatively, the C9 acetate group can be selectively removed byreduction of 10-oxo derivative 11 with a reducing agent such as samariumdiiodide to yield 9-desoxo-10-oxo derivative 12 from which the C13hydroxy protecting group can be selectively removed followed byattachment of a side chain as described above to yield9-desoxo-10-oxo-taxol or other 9-desoxo-10-oxotetracylic taxanes havinga C13 side chain. ##STR15##

Reaction Scheme 4 illustrates a reaction in which 10-DAB is reduced toyield pentaol 13. The C7 and C10 hydroxyl groups of pentaol 13 can thenbe selectively protected with the triethylsilyl or another protectinggroup to produce triol 14 to which a C13 side chain can be attached asdescribed above or, alternatively, after further modification of thetetracylic substituents. ##STR16##

Taxanes having C9 and/or C10 acyloxy substituents other than acetate canbe prepared using 10-DAB as a starting material as illustrated inReaction Scheme 5. Reaction of 10-DAB with triethylsilyl chloride inpyridine yields 7-protected 10-DAB 15. The C10 hydroxy substituent of7-protected 10-DAB 15 may then be readily acylated with any standardacylating agent to yield derivative 16 having a new C10 acyloxysubstituent. Selective reduction of the C9 keto substituent ofderivative 16 yields 9β-hydroxy derivative 17 to which a C13 side chainmay be attached. Alternatively, the C10 and C9 groups can be caused tomigrate as set forth in Reaction Scheme 2, above. ##STR17##

Taxanes having alternative C2 and/or C4 esters can be prepared usingbaccatin III and 10-DAB as starting materials. The C2 and/or C4 estersof baccatin III and 10-DAB can be selectively reduced to thecorresponding alcohol(s) using reducing agents such as LAH or Red-Al,and new esters can thereafter be substituted using standard acylatingagents such as anhydrides and acid chlorides in combination with anamine such as pyridine, triethylamine, DMAP, or diisopropyl ethyl amine.Alternatively, the C2 and/or C4 alcohols may be converted to new C2and/or C4 esters through formation of the corresponding alkoxide bytreatment of the alcohol with a suitable base such as LDA followed by anacylating agent such as an acid chloride.

Baccatin III and 10-DAB analogs having different substituents at C2and/or C4 can be prepared as set forth in Reaction Schemes 6-10. Tosimplify the description, 10-DAB is used as the starting material. Itshould be understood, however, that baccatin III derivatives or analogsmay be produced using the same series of reactions (except for theprotection of the C10 hydroxy group) by simply replacing 10-DAB withbaccatin III as the starting material. 9-desoxo derivatives of thebaccatin III and 10-DAB analogs having different substituents at C2and/or C4 can then be prepared by reducing the C9 keto substituent ofthese analogs and carrying out the other reactions described above.

In Reaction Scheme 6, protected 10-DAB 3 is converted to the triol 18with lithium aluminum hydride. Triol 18 is then converted to thecorresponding C4 ester using Cl₂ CO in pyridine followed by anucleophilic agent (e.g., Grignard reagents or alkyllithium reagents).##STR18##

Deprotonation of triol 18 with LDA followed by introduction of an acidchloride selectively gives the C4 ester. For example, when acetylchloride was used, triol 18 was converted to 1,2 diol 4 as set forth inReaction Scheme 7.

Triol 18 can also readily be converted to the 1,2 carbonate 19.Acetylation of carbonate 19 under vigorous standard conditions providescarbonate 21 as described in Reaction Scheme 8; addition ofalkyllithiums or Grignard reagents to carbonate 19 provides the C2 esterhaving a free hydroxyl group at C4 as set forth in Reaction Scheme 6.##STR19##

As set forth in Reaction Scheme 9, other C4 substituents can be providedby reacting carbonate 19 with an acid chloride and a tertiary amine toyield carbonate 22 which is then reacted with alkyllithiums or Grignardreagents to provide 10-DAB derivatives having new substituents at C2.##STR20##

Alternatively, baccatin III may be used as a starting material andreacted as shown in Reaction Scheme 10. After being protected at C7 andC13, baccatin III is reduced with LAH to produce 1,2,4,10 tetraol 24.Tetraol 24 is converted to carbonate 25 using Cl₂ CO and pyridine, andcarbonate 25 is acylated at C10 with an acid chloride and pyridine toproduce carbonate 26 (as shown) or with acetic anhydride and pyridine(not shown). Acetylation of carbonate 26 under vigorous standardconditions provides carbonate 27 which is then reacted with alkyllithiums to provide the baccatin III derivatives having new substituentsat C2 and C10. ##STR21##

10-desacetoxy derivatives of baccatin III and 10-desoxy derivatives of10-DAB may be prepared by reacting baccatin III or 10-DAB (or theirderivatives) with samarium diiodide. Reaction between the tetracyclictaxane having a C10 leaving group and samarium diiodide may be carriedout at 0° C. in a solvent such as tetrahydrofuran. Advantageously, thesamarium diiodide selectively abstracts the C10 leaving group; C13 sidechains and other substituents on the tetracyclic nucleus remainundisturbed. Thereafter, the C9 keto substituent may be reduced toprovide the corresponding 9-desoxo-9β-hydroxy-10-desacetyoxy or10-desoxy derivatives as otherwise described herein.

C7 dihydro and other C7 substituted taxanes can be prepared as set forthin Reaction Schemes 11, 12 and 12a. ##STR22##

As shown in Reaction Scheme 12, Baccatin III may be converted into7-fluoro baccatin III by treatment with FAR at room temperature in THFsolution. Other baccatin derivatives with a free C7 hydroxyl groupbehave similarly. Alternatively, 7-chloro baccatin III can be preparedby treatment of baccatin III with methane sulfonyl chloride andtriethylamine in methylene chloride solution containing an excess oftriethylamine hydrochloride.

Taxanes having C7 acyloxy substituents can be prepared as set forth inReaction Scheme 12a, 7,13-protected 10-oxo-derivative 11 is converted toits corresponding C13 alkoxide by selectively removing the C13protecting group and replacing it with a metal such as lithium. Thealkoxide is then reacted with a β-lactam or other side chain precursor.Subsequent hydrolysis of the C7 protecting groups causes a migration ofthe C7 hydroxy substituent to C10, migration of the C10 oxo substituentto C9, and migration of the C9 acyloxy substituent to C7.

A wide variety of tricyclic taxanes are naturally occurring, and throughmanipulations analogous to those described herein, an appropriate sidechain can be attached to the C13 oxygen of these substances.Alternatively, as shown in Reaction Scheme 13, 7-O-triethylsilylbaccatin III can be converted to a tricyclic taxane through the actionof trimethyloxonium tetrafluoroborate in methylene chloride solution.The product diol then reacts with lead tetraacetate to provide thecorresponding C4 ketone. ##STR23##

Recently a hydroxylated taxane (14-hydroxy-10-deacetylbaccatin III) hasbeen discovered in an extract of yew needles (C&EN, p 36-37, Apr. 12,1993). Derivatives of this hydroxylated taxane having the various C2,C4, etc. functional groups described above may also be prepared by usingthis hydroxylated taxane. In addition, the C14 hydroxy group togetherwith the C1 hydroxy group of 10-DAB can be converted to a 1,2-carbonateas described in C&EN or it may be converted to a variety of esters orother functional groups as otherwise described herein in connection withthe C2, C4, C7, C9, C10 and C13 substituents.

The following examples are provided to more fully illustrate theinvention.

EXAMPLE 1 ##STR24## Preparation ofN-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-(2-furyl)taxol

To a solution of 7-triethylsilyl baccatin III (120 mg, 0.171 mmol) in1.2 mL of THF at -45° C. was added dropwise 0.104 mL of a 1.63M solutionof nBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(314 mg, 0.885 mmol) in 1.2 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 182 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-N-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-(2-furyl)taxoland a very small amount of the (2'S,3'R)isomer.

To a solution of 182 mg (0.171 mmol) of the mixture obtained from theprevious reaction in 11 mL of acetonitrile and 0.55 mL of pyridine at 0°C. was added 1.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 143 mg of material which was purified byrecrystallization to give 133.0 mg (93%) ofN-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-(2-furyl)taxol.

m.p.155-156° C.; [α]²⁵ _(Na) -73.0° (c 0.0065, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.46 (m, 3H, aromatic), 7.41 (d, J=1.1 Hz, 1H, furyl), 6.38-6.31(m, 2H, furyl), 6.30 (s, 1H, H10), 6.23 (dd, J=9.4, 9.4 Hz, 1H, H13),5.67 (d, J=7.1 Hz, 1H, H2β), 5.3 (d, J=9.3 Hz, 1H, NH), 5.22 (d, J=9.9Hz, 1H, H3'), 4.95 (d, J=9.3 Hz, 1H, H5), 4.71 (br s, 1H, H2'), 4.42 (m,1H, H7), 4.30 (d, J=8.2 Hz, 1H, H20α), 4.16 (d, J=8.2 Hz, 1H, H20β),3.82 (d, J=7.1 Hz, 1H, H3), 3.29 (d, J=5.5 Hz, 1H, 2'OH), 2.56 (m, 1H,H6α), 2.47 (d, J=3.6 Hz, 1H, 7OH), 2.39 (s, 3H, 4Ac), 2.34 (m, 2H, H14),2.24 (s, 3H, 10Ac), 1.90 (m, 1H, H6β), 1.88 (br s, 3H, Me18), 1.70 (s,1H, 1OH), 1.67 (s, 3H, Me19), 1.34 (s, 9H, t-butyl), 1.25 (s, 3H, Me17),1.14 (s, 3H, Me16).

EXAMPLE 2 ##STR25## Preparation ofN-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-(2-furyl)taxol

To a solution of 7-triethylsilyl baccatin III (120 mg, 0.171 mmol) in1.2 mL of THF at -45° C. was added dropwise 0.104 mL of a 1.63M solutionof nBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(ethoxycarbonyl)-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one (290mg, 0.885 mmol) in 1.2 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 179 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-N-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-(2-furyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 179 mg (0.171 mmol) of the mixture obtained from theprevious reaction in 11 mL of acetonitrile and 0.55 mL of pyridine at 0°C. was added 1.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 139 mg of material which as purified by flashchromatography to give 125 mg (90%) ofN-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-(2-furyl)taxol, which wasrecrystallized from methanol/water.

m.p.152-153° C.; [α]²⁵ _(Na) -61.0° (c 0.006, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.65-7.47 (m, 3H, aromatic), 7.42 (s, 1H, furyl), 6.36 (m, 2H, furyl),6.29 (s, 1H, H10), 6.26 (dd, J=8.2, 8.2 Hz, 1H, H13), 5.67 (d, J=7.1 Hz,1H, H2β), 5.37 (br s, 2H, NH, H3'), 4.94 (d, J=8.2 Hz, 1H, H5), 4.72 (d,J=3.3 Hz, 1H, H2'), 4.41 (m, 1H, H7), 4.30 (d, J=8.8 Hz, 1H, H20α), 4.18(d, J=8.8 Hz, 1H, H20β), 4.03 (dd, 14.2, 7.1 Hz, 2H, 0-CH2--), 3.81 (d,J=7.1 Hz, 1H, H3), 3.32 (br s, 1H, 2'OH), 2.54 (m, 1H, H6α), 2.46 (m,1H, 7OH), 2.38 (s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.89(m, 1H, H6β), 1.87 (br s, 3H, Me18), 1.76 (s, 1H, 1OH), 1.67 (s, 3H,Me19), 1.26 (s, 3H, Me17), 1.15 (m, 6H, Me16+Ethyl).

EXAMPLE 3 ##STR26## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(cyclohexyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.094 mL of a 1.68M solution ofnBuLi in hexane. After 1 h at -45° C., a solution ofcis-1-(cyclohexyloxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(275 mg, 0.672 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6 h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 149 mg of a mixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(cyclohexyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 149 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 110 mg of material which was purified by flashchromatography to give 95 mg (81%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(cyclohexyloxycarbonyl)taxol,which was recrystallized from ether/hexane.

m.p. 160-163° C.; [α]²⁵ _(Na) -44.9° (c 0.265, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.14 (d, J=7.2 Hz, 2H, benzoate ortho), 7.62(m, 1H, benzoate, para), 7.51 (t, J=7.2 Hz, 2H, benzoate, meta), 7.29(dd, J=4.8, 1.2 Hz, 1H, thienyl), 7.10 (d, J=3.3 Hz, 1H, thienyl), 7.01(dd, J=4.8, 3.3 Hz, 1H, thienyl), 6.29 (s, 1H, H10), 6.28 (t, J=9.0 Hz,1H, H13), 5.67 (d, J=7.2 Hz, 1H, H2β), 5.56 (d, J=9.3 Hz, 1H, NH), 5.41(dd, J=9.3, 0.9 Hz, 1H, H3'), 4.94 (dd, J=9.3, 1.8 Hz, 1H, H5), 4.66 (d,J=0.9 Hz, 1H, H2'), 4.49 (m, 1H, cyclohexyl), 4.41 (dd, J=11.1, 6.6 Hz,1H, H7), 4.30 (d, J=8.1 Hz, 1H, H20α), 4.17 (d, J=8.1 Hz, 1H, H20β),3.81 (d, J=7.2 Hz, 1H, H3), 3.42 (m, 1H, 2'OH), 2.54 (m, 2H, H6α, 7OH),2.40 (s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.86 (s, 3H,Me18), 1.68 (s, 3H, Me19), 1.26 (s, 3H, Me17), 1.15 (s, 3H, Me16).

EXAMPLE 4 ##STR27## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(t-butoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(274 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(t-butoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 155 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 115 mg (94%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(t-butoxycarbonyl)taxol, whichwas recrystallized from methanol/water.

m.p.151-153° C.; [α]²⁵ _(Na) -64.9° (c 0.0096, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.47 (m, 3H, benzoate), 7.27 (dd, 1H, thienyl), 7.08 (d, J=3.2 Hz,1H, thienyl), 7.01 (m, 1H, thienyl), 6.30 (s, 1H, H10), 6.24 (m, 1H,H13), 5.67 (d, J=7.1 Hz, 1H, H2β)), 5.51 (dd, 1H, H3'), 5.32 (d, J=9.3Hz, 1H, NH), 4.94 (d, J=8.2 Hz, 1H, H5), 4.63 (br s, 1H, H2'), 4.41 (m,1H, H7), 4.30 (d, J=8.8 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β),3.81 (d, J=7.1 Hz, 1H, H3), 3.44 (d, J=3.3 Hz, 1H, 2'OH), 2.53 (m, 1H,H6α), 2.47 (d, J=3.3 Hz, 1H, 7OH), 2.37 (s, 3H, 4Ac), 2.31 (m, 2H, H14),2.23 (s, 3H, 10Ac), 1.90-1.85 (m, 1H, H6β), 1.86 (br s, 3H, Me18), 1.72(s, 1H, 1OH), 1.67 (s, 3H, Me19), 1.33 (br s, 9H, t-butyl), 1.22 (s, 3H,Me17), 1.14 (s, 3H, Me16).

EXAMPLE 5 ##STR28## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(n-butoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(n-butoxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(274 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(n-butoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 155 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 110 mg (90%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(n-butoxycarbonyl)taxol, whichwas recrystallized from methanol/water.

m.p.155-158° C.; [α]²⁵ _(Na) -55.07° (c 0.01, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.00 (m, 6H, aromatic), 6.29 (s, 1H, H10), 6.26 (m, 1H, H13), 5.67(d, J=7.1 Hz, 1H, H2β), 5.56 (d, J=9.3 Hz, 1H, H3'), 5.46 (d, J=9.3 Hz,1H, NH), 4.94 (d, J=7.7 Hz, 1H, H5), 4.66 (br s, 1H, H2'), 4.41 (m, 1H,H7), 4.30 (d, J=8.2 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β), 3.96(m, 2H, butyl), 3.80 (d, J=7.1 Hz, 1H, H3), 3.45 (d, J=5.0 Hz, 1H,2'OH), 2.53 (m, 1H, H6α), 2.47 (br m, 1H, 7OH), 2.38 (s, 3H, 4Ac), 2.31(m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.92 (d, 1H, 1OH), 1.87 (m, 1H, H6β),1.84 (br s, 3H, Me18), 1.68 (s, 3H, Me19), 1.49 (m, 2H, butyl), 1.26 (s,3H, Me17), 1.21 (m, 2H, butyl), 1.14 (s, 3H, Me16), 0.82 (t, 3H,Me-butyl).

EXAMPLE 6 ##STR29## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(allyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(allyloxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(263 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 153 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(allyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 153 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 120 mg of material which was purified by flashchromatography to give 105 mg (87%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(allyloxycarbonyl)taxol, whichwas recrystallized from methanol/water.

m.p.137-139° C.; [α]²⁵ _(Na) -58.81° (c 0.006, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=7.1 Hz, 2H, benzoate ortho),7.60-7.00 (m, 6H, aromatic), 6.28 (s, 1H, H10), 6.25 (m, 1H, H13), 5.80(m, 1H, allylic), 5.67 (d, J=7.1 Hz, 1H, H2β), 5.56 (br s, 2H, NH &H3'), 5.21 (m, 2H, allylic), 4.94 (dd, J=9.3, 1.7 Hz, 1H, H5), 4.67 (brs, 1H, H2'), 4.47-4.38 (m, 3H, H7 & allylic), 4.30 (d, J=8.2 Hz, 1H,H20α), 4.18 (d, J=8.2 Hz, 1H, H20β), 3.80 (d, J=7.1 Hz, 1H, H3), 3.46(br s, 1H, 2'OH), 2.56 (m, 1H, H6α), 2.38 (s, 3H, 4Ac), 2.31 (m, 2H,H14), 2.24 (s, 3H, 10Ac), 1.89 (m, 1H, H6β), 1.84 (br s, 3H, Me18), 1.74(br s, 1H, 7 OH), 1.68 (s, 3H, Me19), 1.60 (br s, 1H, 1 OH), 1.26 (s,3H, Me17), 1.14 (s, 3H, Me16).

EXAMPLE 7 ##STR30## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(isobutoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-isobutoxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(263 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 153 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-isobutoxycarbonyltaxol and a small amount of the (2'S,3'R)isomer.

To a solution of 153 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 120 mg of material which was purified by flashchromatography to give 100 mg (83%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-isobutoxycarbonyl taxol, whichwas recrystallized from methanol/water.

m.p. 147-148° C.; [α]²⁵ _(Na) -62.4° (c 1.035, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=7.2 Hz, 2H, benzoate ortho), 7.62(m, 1H, aromatic), 7.51 (t, J=7.2 Hz, 2H, aromatic), 7.43 (d, J=1.2 Hz,1H, furyl), 6.39 (dd, J=3.0, 1.2 Hz, 1H, furyl), 6.35 (d, J=3.0 Hz, 1H,furyl), 6.31 (s, 1H, H10), 6.27 (dd, J=8.7, 8.7 Hz, 1H, H13), 5.69 (d,J=7.2 Hz, 1H, H2β), 5.41 (m, 2H, NH, H3'), 4.95 (dd, J=9.6, 2.1 Hz, 1H,H5), 4.75 (d, J=5.4 Hz, 1H, H2'), 4.43 (m, 1H, H7), 4.31 (d, J=8.7 Hz,1H, H20α), 4.18 (d, J=8.7 Hz, 1H, H20β), 3.82 (d, J=7.2 Hz, 1H, H3),3.75 (m, 2H, isobutyl), 3.35 (d, J=5.4 Hz, 2OH), 2.55 (m, 1H, H6α), 2.49(d, J=4.5 Hz, 7OH), 2.40 (s, 3H, 4Ac), 2.36 (m, 2H, H14), 2.25 (s, 3H,10Ac), 1.92 (m, 1H, H6β), 1.88 (s, 3H, Me18), 1.84 (m, 1H, isobutyl),1.77 (s, 1H, 1OH), 1.68 (s, 3H, Me19), 1.27 (s, 3H, Me17), 1.16 (s, 3H,Me16), 0.83 (d, J=7.5, 3H, isobutyl), 0.81 (d, J=7.5 Hz, 3H, isobutyl).

EXAMPLE 8 ##STR31## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(butoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-n-butoxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one (263mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 153 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-n-butoxycarbonyltaxol and a small amount of the (2'S,3'R)isomer.

To a solution of 153 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 121 mg of material which was purified by flashchromatography to give 90 mg (75%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-n-butoxycarbonyl taxol, whichwas recrystallized from methanol/water.

m.p. 145-146.5° C.; [α]²⁵ _(Na) -63.0° (c 1.000, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=6.9 Hz, 2H, benzoate ortho), 7.62(m, 1H, benzoate, para), 7.51 (t, J=6.9 Hz, 2H, benzoate, meta), 7.43(d, J=1.2 Hz, 1H, furyl), 6.40 (dd, J=3.0, 1.2 Hz, 1H, furyl), 6.35 (d,J=3.0 Hz, 1H, furyl), 6.31 (s, 1H, H10), 6.28 (m, 1H, H13), 5.69 (d,J=7.5 Hz, 1H, H2β), 5.38 (m, 2H, NH, H3'), 4.96 (dd, J=9.3, 2.4 Hz, 1H,H5), 4.74 (d, J=5.1 Hz, 1H, H2'), 4.43 (m, 1H, H7), 4.31 (d, J=8.1 Hz,1H, H20α), 4.19 (d, J=8.1 Hz, 1H, H20β), 3.98 (m, 2H, butyl), 3.83 (d,J=7.2 Hz, 1H, H3), 3.29 (d, J=5.1 Hz, 2'OH), 2.55 (m, 1H, H6α), 2.46 (d,J=3.9 Hz, 7OH), 2.40 (s, 3H, 4Ac), 2.36 (m, 2H, H14), 2.25 (s, 3H,10Ac), 1.93 (m, 1H, H6β), 1.89 (s, 3H, Me18), 1.72 (s, 1H, 1OH), 1.69(s, 3H, Me19), 1.52 (m, 4H, butyl), 1.28 (s, 3H, Me17), 1.16 (s, 3H,Me16), 0.84 (t, J=7.2, 3H, butyl).

EXAMPLE 9 ##STR32## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(isopropoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-isopropoxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(254 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 151 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-dephenyl-3'-(2-furyl)-N-isopropoxycarbonyltaxol and a small amount of the (2'S,3'R)isomer.

To a solution of 151 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 118 mg of material which was purified by flashchromatography to give 108 mg (92%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-isopropoxycarbonyl taxol, whichwas recrystallized from methanol/water.

m.p. 184-185° C.; [α]²⁵ _(Na) -62.9° (c 1.015, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=7.2 Hz, 2H, benzoate, meta), 7.43(d, J=1.8 Hz, 1H, furyl), 6.38 (dd, J=3.3, 1.8 Hz, 1H, furyl), 6.33 (d,J=3.3 Hz, 1H, furyl), 6.30 (s, 1H, H10), 6.26 (t, J=9.0 Hz, 1H, H13),5.68 (d, J=6.9 Hz, 1H, H2β), 5.33 (m, 2H, NH, H3'), 4.95 (dd, J=7.2, 2.1Hz, 1H, H5), 4.79 (m, 1H, isopropyl), 4.73 (br s, 1H, H2'), 4.42 (dd,J=10.2, 6.0 Hz, 1H, H7), 4.31 (d, J=8.4 Hz, 1H, H20α), 4.17 (d, J=8.4Hz, 1H, H20β), 3.82 (d, J=6.9 Hz, 1H, H3), 3.33 (m, 1H, 2'OH), 2.55 (m,2H, H6α, 7OH), 2.39 (s, 3H, 4Ac), 2.33 (m, 2H, H14), 2.24 (s, 3H, 10Ac),1.93 (m, 1H, H6β), 1.88 (s, 3H, Me18), 1.83 (s, 1H, 1OH), 1.68 (s, 3H,Me19), 1.26 (s, 3H, Me17), 1.18 (d, J=6.3 Hz, 3H, isopropyl), 1.16 (s,3H, Me16), 1.11 (d, J=6.3 Hz, 3H, isopropyl).

EXAMPLE 10 ##STR33## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(allyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-allyloxycarbonyl-3-triethyl-silyloxy-4-(2-furyl)azetidin-2-one(251 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 150 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-allyloxycarbonyltaxol and a small amount of the (2'S,3'R)isomer.

To a solution of 150 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 118 mg of material which was purified by flashchromatography to give 100 mg (85%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-allyloxycarbonyl taxol, whichwas recrystallized from methanol/water.

m.p. 143-145° C.; [α]²⁵ _(Na) -65.0° (c 1.000, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=7.2 Hz, 2H, benzoate, meta), 7.43(d, J=2.1 Hz, 1H, furyl), 6.39 (dd, J=3.3, 2.1 Hz, 1H, furyl), 6.35 (d,J=3.3 Hz, 1H, furyl), 6.30 (s, 1H, H10), 6.27 (t, J=9.0 Hz, 1H, H13),5.82 (m, 1H, allyl), 5.68 (d, J=7.2 Hz, 1H, H2β), 5.51 (d, J=9.8 Hz, 1H,H3'), 5.40 (d, J=9.8 Hz, 1H, NH), 5.15 (m, 2H, allyl), 4.95 (dd, J=9.3,1.5 Hz, 1H, H5), 4.75 (br s, 1H, H2'), 4.48 (d, J=5.4 Hz, 2H, allyl),4.42 (m, 1H, H7), 4.30 (d, J=8.2 Hz, 1H, H20α), 4.18 (d, J=8.2 Hz, 1H,H20β), 3.82 (d, J=7.2 Hz, 1H, H3), 3.37 (d, J=5.4 Hz, 2'OH), 2.55 (m,2H, H6α, 7OH), 2.39 (s, 3H, 4Ac), 2.33 (m, 2H, H14), 2.25 (s, 3H, 10Ac),1.93 (m, 1H, H6β), 1.88 (s, 3H, Me18), 1.78 (s, 1H, 1OH), 1.69 (s, 3H,Me19), 1.26 (s, 3H, Me17), 1.16 (s, 3H, Me16).

EXAMPLE 11 ##STR34## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(benzyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-benzyloxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(287 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 158 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-benzyloxycarbonyltaxol and a small amount of the (2'S,3'R)isomer.

To a solution of 158 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 125 mg of material which was purified by flashchromatography to give 107 mg (86%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-benzyloxycarbonyl taxol, whichwas recrystallized from methanol/water.

m.p. 164-165° C.; [α]²⁵ _(Na) -54.8° (c 1.030, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=6.9 Hz, 2H, benzoate ortho), 7.60(m, 1H, benzoate, para), 7.50 (t, J=6.9 Hz, 2H, benzoate, meta), 7.42(d, J=1.2 Hz, 1H, furyl), 7.27 (m, 2H, benzyl), 7.18 (m, 3H, benzyl),6.38 (dd, J=3.3, 1.2 Hz, 1H, furyl), 6.34 (d, J=3.3 Hz, 1H, furyl), 6.27(s, 1H, H10), 6.23 (t, J=9.3 Hz, 1H, H13), 5.65 (d, J=7.2 Hz, 1H, H2β),5.54 (d, J=9.3 Hz, 1H, H3'), 5.42 (d, J=9.3 Hz, 1H, NH), 4.99 (m, 3H,benzyl, H5), 4.73 (br s, 1H, H2'), 4.41 (m, 1H, H7), 4.29 (d, J=8.7 Hz,1H, H20α), 4.19 (d, J=8.7 Hz, 1H, H20β), 3.79 (d, J=7.2 Hz, 1H, H3),3.34 (d, J=4,8 Hz, 2'OH), 2.54 (m, 1H, H6α), 2.45 (m, 1H, 7OH), 2.38 (s,3H, 4Ac), 2.32 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.92 (m, 1H, H6β), 1.85(s, 3H, Me18), 1.68 (s, 3H, Me19), 1.60 (s, 1H, 1OH), 1.22 (s, 3H,Me17), 1.14 (s, 3H, Me16).

EXAMPLE 12 ##STR35## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(ethoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.094 mL of a 1.68M solution ofnBuLi in hexane. After 1 h at -45° C., a solution ofcis-1-(ethoxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(254 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 114 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(ethoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 114 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 110 mg of material which was purified by flashchromatography to give 69 mg (78%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(ethoxycarbonyl)taxol, whichwas recrystallized from ethyl acetate.

m.p. 240-243° C.; [α]²⁵ _(Na) -60.0° (c 0.255, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=7.8 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=7.8 Hz, 2H, benzoate, meta), 7.29(d, J=5.1 Hz, 1H, thienyl), 7.11 (d, J=3.3 Hz, 1H, thienyl), 7.01 (dd,J=5.1, 3.3 Hz, 1H, thienyl), 6.29 (s, 1H, H10), 6.28 (br t, J=9.0 Hz,1H, H13), 5.67 (d, J=6.9 Hz, 1H, H2β), 5.55 (br d, J=9.3 Hz, 1H, NH),5.45 (d, J=9.3, 1H, H3'), 4.94 (dd, J=9.3, 2.4 Hz, 1H, H5), 4.66 (br s,1H, H2'), 4.41 (dd, J=11.1, 6.6 Hz, 1H, H7), 4.30 (d, J=8.1 Hz, 1H,H20α), 4.18 (d, J=8.1 Hz, 1H, H20β), 4.01 (q, J=7.2 Hz, CH2), 3.81 (d,J=6.9 Hz, 1H, H3), 3.45 (br s, 1H, 2'OH), 2.54 (m, 2H, H6α and 7OH),2.38 (s, 3H, 4Ac), 2.24 (s, 3H, 10Ac), 1.84 (d, J=0.9 Hz, 3H, Me18),1.68 (s, 3H, Me19), 1.25 (s, 3H, Me17), 1.15 (s, 3H, Me16), 1.14 (t,J=7.2 Hz, 3H, Me).

EXAMPLE 13 ##STR36## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(3-butynyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (91 mg, 0.13 mmol) in 1 mLof THF at -45° C. was added dropwise 0.085 mL of a 1.68M solution ofnBuLi in hexane. After 1 h at -45° C., a solution ofcis-1-(3-butynyloxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(197 mg, 0.52 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6 h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 60 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(3-butynyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 60 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 44 mg of material which was purified by flashchromatography to give 42 mg (89%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(3-butynyloxycarbonyl)taxol,which was recrystallized from ether/hexane.

m.p. 148-149° C.; [α]²⁵ _(Na) -50.79° (c 1.40, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=7.2 Hz, 2H, benzoate ortho), 7.62(t, J=7.2 Hz, 1H, benzoate, para), 7.51 (t, J=7.2 Hz, 2H, benzoate,meta), 7.30 (dd, J=5.4, 0.9 Hz, 1H, thienyl), 7.12 (dd, J=3.3, 0.9 Hz,1H, thienyl), 7.02 (dd, J=5.4, 3.3 Hz, 1H, thienyl), 6.29 (m, 2H, H10and H13), 5.67 (d, J=6.9 Hz, 1H, H2β), 5.56 (br s, 2H, NH and H3'), 4.94(dd, J=9.6, 1.8 Hz, 1H, H5), 4.67 (d, J=3.9 Hz, 1H, H2'), 4.41 (m, 1H,H7), 4.31 (d, J=8.7 Hz, 1H, H20α), 4.18 (d, J=8.7 Hz, 1H, H20β), 4.07(t, J=6.6 Hz, 2H, CH2), 3.81 (d, J=6.9 Hz, 1H, H3), 3.46 (br s, 1H,2'OH), 2.55 (m, 1H, H6α), 2.38 (s, 3H, 4Ac), 2.24 (s, 3H, 10Ac), 1.95(t, J=2.7 Hz, 1H, acetylene), 1.85 (s, 3H, Me18), 1.68 (s, 3H, Me19),1.26 (s, 3H, Me17), 1.15 (s, 3H, Me16).

EXAMPLE 14 ##STR37## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(crotyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (91 mg, 0.13 mmol) in 1 mLof THF at -45° C. was added dropwise 0.085 mL of a 1.68M solution ofnBuLi in hexane. After 1 h at -45° C., a solution ofcis-1-(crotyloxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(198 mg, 0.52 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6 h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 96 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(crotyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 96 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 65 mg of material which was purified by flashchromatography to give 62 mg (81%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(crotyloxycarbonyl)taxol,which was recrystallized from ether/hexane.

m.p. 143-145° C.; [α]²⁵ _(Na) -54.37° (c 0.675, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (dd, J=8.1, 0.9 Hz, 2H, benzoate ortho),7.61 (m, 1H, benzoate, para), 7.50 (m, 2H, benzoate, meta), 7.29 (dd,J=5.1, 1.2 Hz, 1H, thienyl), 7.11 (br d, J=3.3 Hz, 1H, thienyl), 7.01(dd, J=5.1, 3.3 Hz, 1H, thienyl), 6.29 (s, 1H, H10), 6.27 (br t, J=7.5Hz, 1H, H13), 5.67 (d, J=6.9 Hz, 1H, H2β), 5.66-5.42 (m, 4H, H3', NH andcrotyl), 4.94 (dd, J=9.9, 2.1 Hz, 1H, H5), 4.66 (m, 1H, H2'), 4.40 (m,3H, H7 and CH₂), 4.30 (d, J=8.4 Hz, 1H, H20α), 4.18 (d, J=8.4 Hz, 1H,H20β), 3.81 (d, J=6.9 Hz, 1H, H3), 3.44 (d, J=5.1 Hz, 1H, 2'OH), 2.54(m, 1H, H6α), 2.38 (s, 3H, 4Ac), 2.24 (s, 3H, 10Ac), 1.84 (d, J=1.2 Hz,3H, Me18), 1.68 (s, 3H, Me19), 1.64 (br d, J=6.0 Hz, 3H, Me), 1.26 (s,3H, Me17), 1.15 (s, 3H, Me16).

EXAMPLE 15 ##STR38## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(1,3-diethoxy-2-propoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution of(TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(1,3-diethoxy-2-propoxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(327 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6 h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 136 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(1,3-diethoxy-2-propoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 136 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 106 mg of material which was purified by flashchromatography to give 103 mg (94%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(1,3-diethoxy-2-propoxycarbonyl)taxol,which was recrystallized from ethyl acetate/hexane. m.p. 202-203° C.;[α]²⁵ _(Na) -44.78° (c 0.67, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.15 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=7.2 Hz, 2H, benzoate, meta), 7.29(dd, J=4.8, 0.9 Hz, 1H, thienyl), 7.10 (br d, J=3.3 Hz, 1H, thienyl),7.01 (dd, J=4.8, 3.3 Hz, 1H, thienyl), 6.30 (m, 1H, H13), 6.28 (s, 1H,H10), 5.68 (d, J=6.9 Hz, 1H, H2β), 5.59 (m, 2H, NH and H3'), 4.94 (dd,J=9.9, 2.1 Hz, 1H, H5), 4.81 (m, 1H, CH), 4.66 (br s, 1H, H2'), 4.41(dd, J=11.1, 6.6 Hz, 1H, H7), 4.30 (d, J=8.4 Hz, 1H, H20α), 4.20 (d,J=8.4 Hz, 1H, H20β), 3.81 (d, J=6.9 Hz, 1H, H3), 3.41 (m, 9H, CH2×4 and2'OH), 2.54 (m, 1H, H6α), 2.41 (s, 3H, 4Ac), 2.24 (s, 3H, 10Ac), 1.85(d, J=1.2 Hz, 3H, Me18), 1.68 (s, 3H, Me19), 1.25 (s, 3H, Me17), 1.15(s, 3H, Me16), 1.12 (t, J=7.2 Hz, 3H, Me), 1.08 (t, J=7.2 Hz, 3H, Me).

EXAMPLE 16 ##STR39## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.085 mL of a 1.68M solution ofnBuLi in hexane. After 1 h at -45° C., a solution ofcis-1-(2-methoxyethoxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(270 mg, 0.701 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6 h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 130 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 130 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 104 mg of material which was purified by flashchromatography to give 98 mg (95%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxol,which was recrystallized from ethyl acetate/ether/hexane.

m.p. 144-145° C.; [α]²⁵ _(Na) -46.15° (c 2.195, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.14 (d, J=7.2 Hz, 2H, benzoate ortho), 7.58(m, 1H, benzoate, para), 7.51 (t, J=7.2 Hz, 2H, benzoate, meta), 7.29(d, J=3.9 Hz, 1H, thienyl), 7.11 (d, J=3.3 Hz, 1H, thienyl), 7.02 (dd,J=3.9, 3.3 Hz, 1H, thienyl), 6.28 (m, 2H, H10 and H13), 5.68 (d, J=7.2Hz, 1H, H2β), 5.58 (br s, 2H, NH and H3'), 4.94 (d, J=7.8 Hz, 1H, H5),4.66 (s, 1H, H2'), 4.41 (m, 1H, H7), 4.31 (d, J=8.1 Hz, 1H, H20α), 4.19(d, J=8.1 Hz, 1H, H20β), 4.10 (m, 2H, CH2), 3.81 (d, J=7.2 Hz, 1H, H3),3.42 (m, 3H, CH2 and 2'OH), 3.30 (s, 3H, OMe), 2.54 (m, 1H, H6α), 2.40(s, 3H, 4Ac), 2.24 (s, 3H, 10Ac), 1.85 (s, 3H, Me18), 1.68 (s, 3H,Me19), 1.26 (s, 3H, Me17), 1.15 (s, 3H, Me16).

EXAMPLE 17 ##STR40## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(neopentyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0M solution of(TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(neopentyloxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(284 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6 h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 145 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(neopentyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 145 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 113 mg of material which was purified by flashchromatography to give 106 mg (94%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(neopentyloxycarbonyl)taxol,which was recrystallized from ethyl acetate/ether/hexane.

m.p. 163-165° C.; [α]²⁵ _(Na) -52.42° (c 0.62, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=7.5 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=7.5 Hz, 2H, benzoate, meta), 7.29(d, J=3.9 Hz, 1H, thienyl), 7.11 (d, J=3.3 Hz, 1H, thienyl), 7.02 (dd,J=3.9, 3.3 Hz, 1H, thienyl), 6.29 (s, 1H, H10), 6.25 (br t, J=9.9 Hz,1H, H13), 5.67 (d, J=7.2 Hz, 1H, H2β), 5.53 (m, 2H, NH and H3'), 4.94(dd, J=9.3, 1.5 Hz, 1H, H5), 4.67 (d, J=3.9 Hz, 1H, H2'), 4.41 (m, 1H,H7), 4.30 (d, J=8.4 Hz, 1H, H20α), 4.17 (d, J=8.4 Hz, 1H, H20β), 3.80(d, J=7.2 Hz, 1H, H3), 3.71 (d, J=10.2 Hz, 1H, t-BuCH), 3.63 (d, J=10.2Hz, 1H, t-BuCH), 3.50 (d, J=3.9 Hz, 1H, 2'OH), 2.54 (m, 2H, H6α, 7OH),2.39 (s, 3H, 4Ac), 2.24 (s, 3H, 10Ac), 1.85 (s, 3H, Me18), 1.77 (s, 1H,1OH), 1.67 (s, 3H, Me19), 1.25 (s, 3H, Me17), 1.14 (s, 3H, Me16), 0.81(s, 9H, tBu).

EXAMPLE 18 ##STR41## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(isopropoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(isopropoxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(264 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 153 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(isopropoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 153 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 120 mg of material which was purified by flashchromatography to give 109 mg (90%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(isopropoxycarbonyl)taxol,which was recrystallized from methanol/water.

m.p.201-203° C.; [α]²⁵ _(Na) -64.4° (c 0.005, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.64-6.99 (m, 6H, aromatic), 6.31-6.23 (br m, 2H, H10 & H13), 5.67 (d,J=7.1 Hz, 1H, H2b)), 5.54 (dd, 1H, H3'), 5.40 (d, J=9.3 Hz, 1H, NH),4.95 (d, J=7.7 Hz, 1H, H5), 4.78 (m, 1H, isopropyl), 4.66 (d, 1H, H2'),4.42 (m, 1H, H7), 4.30 (d, J=8.2 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H,H20β), 3.81 (d, J=7.1 Hz, 1H, H3), 3.47 (d, J=5.5 Hz, 1H, 2'OH), 2.53(m, 1H, H6α), 2.48 (br m, 1H, 7OH), 2.38 (s, 3H, 4Ac), 2.31 (m, 2H,H14), 2.24 (s, 3H, 10Ac), 1.87 (m, 1H, H6β), 1.84 (br s, 3H, Me18), 1.68(s, 3H, Me19), 1.26 (s, 3H, Me17), 1.14 (s, 3H, Me16), 1.08 (d, J=6 Hz,6H, isopropyl)

EXAMPLE 19 ##STR42## Preparation of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(isobutoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(isobutoxycarbonyl)-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(274 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(isobutoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 155 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 107 mg (88%) of3'-desphenyl-3'-(2-thienyl)-N-debenzoyl-N-(isobutoxycarbonyl)taxol,which was recrystallized from methanol/water.

m.p.172-175° C.; [α]²⁵ _(Na) -63.4° (c 0.0054, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=7.7 Hz, 2H, benzoate ortho),7.63-6.99 (m, 6H, aromatic), 6.28 (s, 1H, H10), 6.27-6.23 (m, 1H, H13),5.67 (d, J=7.1 Hz, 1H, H2β)), 5.57-5.47 (m, 2H, H3' & NH), 4.93 (d,J=7.7 Hz, 1H, H5), 4.66 (br s, 1H, H2'), 4.41 (m, 1H, H7), 4.30 (d,J=8.2 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β), 3.81-3.68 (m, 3H,butyl & H3), 3.48 (br m, 1H, 2'OH), 2.53 (m, 1H, H6α), 2.38 (s, 3H,4Ac), 2.30 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.84 (br s, 3H, Me18), 1.78(m, 1H, H6β), 1.68 (s, 3H, Me19), 1.26 (s, 3H, Me17), 1.14 (s, 3H,Me16), 0.80 (t, 6H, isobutyl).

EXAMPLE 20 ##STR43## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(2-methoxyethoxycarbonyl)-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(264 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 153 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 153 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 120 mg of material which was purified by flashchromatography to give 107 mg (89%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxol,which was recrystallized from methanol/water.

m.p. 161-162° C.; [α]²⁵ _(Na) -55.0° (c 0.500, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=7.2 Hz, 2H, benzoate ortho), 7.59(m, 1H, benzoate, para), 7.49 (t, J=7.2 Hz, 2H, benzoate, meta), 7.41(d, J=1.2 Hz, 1H, furyl), 6.37 (dd, J=3.3, 1.2 Hz, 1H, furyl), 6.33 (d,J=3.3 Hz, 1H, furyl), 6.29 (s, 1H, H10), 6.27 (t, J=8.7 Hz, 1H, H13),5.67 (d, J=7.2 Hz, 1H, H2β), 5.61 (m, 1H, H3'), 5.38 (d, J=8.7 Hz, 1H,NH), 4.94 (dd, J=9.6, 1.8 Hz, 1H, H5), 4.73 (br s, 1H, H2'), 4.41 (dd,J=10.5, 6.6 Hz, 1H, H7), 4.29 (d, J=8.4 Hz, 1H, H20α), 4.18 (d, J=8.4Hz, 1H, H20β), 4.11 (m, 2H, methoxyethyl), 3.80 (d, J=7.2 Hz, 1H, H3),3.43 (m, 3H, 2'OH, methoxyethyl), 2.53 (m, 2H, H6α, 7OH), 2.39 (s, 3H,4Ac), 2.32 (m, 2H, H14), 2.23 (s, 3H, 10Ac), 2.19 (m, 1H, H6β), 1.92 (m,1H, 1OH), 1.86 (s, 3H, Me18), 1.67 (s, 3H, Me19), 1.23 (s, 3H, Me17),1.12 (s, 3H, Me16).

EXAMPLE 21 ##STR44## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(crotyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(crotyloxycarbonyl)-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(261 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 152 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(crotyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 152 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 120 mg of material which was purified by flashchromatography to give 107 mg (89%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(crotyloxycarbonyl)taxol, whichwas recrystallized from methanol/water.

m.p. 128-129° C.; [α]²⁵ _(Na) -64.7° (c 0.510, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.5 Hz, 2H, benzoate ortho), 7.59(m, 1H, benzoate, para), 7.48 (t, J=7.5 Hz, 2H, benzoate, meta), 7.41(d, J=1.5 Hz, 1H, furyl), 6.36 (dd, J=3.3, 1.5 Hz, 1H, furyl), 6.33 (d,J=3.3 Hz, 1H, furyl), 6.28 (s, 1H, H10), 6.26 (t, J=9.0 Hz, 1H, H13),5.66 (m, 2H, H2β, crotyl), 5.50 (m, 1H, H3'), 5.41 (m 2H, NH, crotyl),4.93 (dd, J=9.6, 1.8 Hz, 1H, H5), 4.72 (br s, 1H, H2'), 4.41 (m, 3H, H7,crotyl), 4.29 (d, J=8.1 Hz, 1H, H20α), 4.16 (d, J=8.1 Hz, 1H, H20β),3.80 (d, J=7.2 Hz, 1H, H3), 3.33 (br s, 1H, 2'OH), 2.54 (m, 2H, H6α,7OH), 2.37 (s, 3H, 4Ac), 2.32 (m, 2H, H14), 2.23 (s, 3H, 10Ac), 1.86 (s,3H, Me18), 1.83 (m, 1H, H6β), 1.73 (br s, 1H, 1OH), 1.67 (s, 3H, Me19),1.63 (d, J=6.6 Hz, 3H, crotyl), 1.25 (s, 3H, Me17), 1.14 (s, 3H, Me16).

EXAMPLE 22 ##STR45## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(neopentyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-neopentyloxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(273 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-neopentyloxycarbonyltaxol and a small amount of the (2'S,3'R)isomer.

To a solution of 155 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 122 mg of material which was purified by flashchromatography to give 105 mg (86%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-neopentyloxycarbonyl taxol,which was recrystallized from methanol/water.

m.p. 145-146.5° C.; [α]²⁵ _(Na) -57.0° (c 0.470, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=6.9 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=6.9 Hz, 2H, benzoate, meta), 7.43(d, J=1.8 Hz, 1H, furyl), 6.39 (dd, J=3.3, 1.8 Hz, 1H, furyl), 6.34 (d,J=3.3 Hz, 1H, furyl), 6.30 (s, 1H, H10), 6.26 (t, J=7.8, 1H, H13), 5.67(d, J=7.2 Hz, 1H, H2β), 5.41 (br s, 2H, H3', NH), 4.95 (dd, J=6.9, 2.1Hz, 1H, H5), 4.75 (br s, 1H, H2'), 4.43 (m, 1H, H7), 4.30 (d, J=8.4 Hz,1H, H20α), 4.18 (d, J=8.4 Hz, 1H, H20β), 3.81 (d, J=7.2 Hz, 1H, H3),3.74 (d, J=9.9 Hz, 1H, neopentyl), 3.65 (d, J=neopentyl), 3.32 (d, J=6.0Hz, 1H, 2'OH), 2.55 (m, 1H, H6α), 2.47 (m, 1H, 7OH), 2.40 (s, 3H, 4Ac),2.29 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.88 (s, 3H, Me18), 1.83 (m, 1H,H6β), 1.75 (s, 1OH), 1.68 (s, 3H, Me19), 1.26 (s, 3H, Me17), 1.15 (s,3H, Me16), 0.83 (s, 9H, neopentyl).

EXAMPLE 23 ##STR46## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(cyclohexyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(cyclohexyloxycarbonyl)-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(272 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(cyclohexyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 155 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 122 mg of material which was purified by flashchromatography to give 105 mg (86%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(cyclohexyloxycarbonyl taxol,which was recrystallized from methanol/water.

m.p. 133-134° C.; [α]²⁵ _(Na) -59.6° (c 0.500, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=7.2 Hz, 2H, benzoate ortho), 7.60(m, 1H, benzoate, para), 7.49 (t, J=7.2 Hz, 2H, benzoate, meta), 7.41(d, J=1.2 Hz, 1H, furyl), 6.37 (dd, J=3.3, 1.2 Hz, 1H, furyl), 6.33 (d,J=3.3 Hz, 1H, furyl), 6.30 (s, 1H, H10), 6.25 (t, J=7.5 Hz, 1H, H13),5.66 (d, J=7.2 Hz, 1H, H2β), 5.38 (br s, 2H, H3', NH), 4.94 (dd, J=9.3,2.1 Hz, 1H, H5), 4.73 (d, J=4.8 Hz, 1H, H2'), 4.49 (m, 1H,cyclohexanyl), 4.42 (m, 1H, H7), 4.28 (d, J=8.7 Hz, 1H, H20α), 4.17 (d,J=8.7 Hz, 1H, H20β), 3.81 (d, J=7.2 Hz, 1H, H3), 3.38 (d, J=4.8 Hz, 1H,2'OH), 2.57 (m, 1H, H6α), 2.49 (m, 1H, 7OH), 2.39 (s, 3H, 4Ac), 2.32 (m,2H, H14), 2.23 (s, 3H, 10Ac), 1.92 (m, 1H, 1OH), 1.88 (s, 3H, Me18),1.83 (m, 1H, H6β), 1.74 (m, 4H, cyclohexanyl), 1.67 (s, 3H, Me19), 1.53(m, 4H, cyclohexanyl), 1.29 (m, 2H, cyclohexanyl), 1.26 (s, 3H, Me17),1.14 (s, 3H, Me16).

EXAMPLE 24 ##STR47## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(1,3-diethoxy-2-propyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(1,3-diethoxy-2-propyloxycarbonyl)-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(316 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 163 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(1,3-diethoxy-2-propyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 163 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 131 mg of material which was purified by flashchromatography to give 116 mg (89%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(1,3-diethoxy-2-propyloxycarbonyl)taxol,which was recrystallized from methanol/water.

m.p. 120-121° C.; [α]²⁵ _(Na) -57.5° (c 0.510, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.13 (d, J=7.2 Hz, 2H, benzoate ortho), 7.60(t, J=7.2 Hz, 1H, benzoate, para), 7.49 (t, J=7.2 Hz, 2H, benzoate,meta), 7.42 (br s, 1H, furyl), 6.37 (br s, 1H, furyl), 6.33 (d, J=2.7Hz, 1H, furyl), 6.29 (s, 1H, H10), 6.26 (m, 1H, H13), 5.68 (d, J=7.2 Hz,1H, H2β), 5.57 (d, J=9.9 Hz, 1H, H3'), 5.39 (d, J=9.9 Hz, 1H, NH), 4.94(d, J=8.1 Hz, 1H, H5), 4.84 (t, J=5.1 Hz, 1H, 1,3-diethoxypropyl), 4.73(br s, 1H, H2'), 4.42 (m, 1H, H7), 4.29 (d, J=8.1 Hz, 1H, H20α), 4.18(d, J=8.1 Hz, 1H, H20β), 3.81 (d, J=7.2 Hz, 1H, H3), 3.44 (m, 9H, 2'OH,1,3-diethoxypropyl), 2.54 (m, 1H, H6α), 2.48 (m, 1H, 7OH), 2.40 (s, 3H,4Ac), 2.34 (m, 2H, H14), 2.23 (s, 3H, 10Ac), 1.92 (s, 1OH), 1.87 (s, 3H,Me18), 1.83 (m, 1H, H6β), 1.67 (s, 3H, Me19), 1.25 (s, 3H, Me17), 1.14(m, 6H, Me16, 1,3-diethoxy-propyl), 1.08 (t, J=6.6 Hz, 3H,1,3-diethoxypropyl).

EXAMPLE 25 ##STR48## Preparation of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(3-butynyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(3-butynyloxycarbonyl)-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(256 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 152 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(3-butynyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 152 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 119 mg of material which was purified by flashchromatography to give 101 mg (85%) of3'-desphenyl-3'-(2-furyl)-N-debenzoyl-N-(3-butynyloxycarbonyl)taxol,which was recrystallized from methanol/water.

m.p. 148-148° C.; [α]²⁵ _(Na) -58.8° (c 0.480, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(t, J=7.2 Hz, 1H, benzoate, para), 7.50 (t, J=7.2 Hz, 2H, benzoate,meta), 7.42 (d, J=1.2 Hz, 1H, furyl), 6.38 (dd, J=3.3, 1.8 Hz, 1H,furyl), 6.35 (d, J=3.3 Hz, 1H, furyl), 6.30 (s, 1H, H10), 6.28 (m, 1H,H13), 5.67 (d, J=7.2 Hz, 1H, H2β), 5.52 (d, J=9.9 Hz, 1H, H3'), 5.38 (d,J=9.9 Hz, 1H, NH), 4.94 (d, J=7.8 Hz, 1H, H5), 4.73 (br s, 1H, H2'),4.42 (m, 1H, H7), 4.29 (d, J=8.7 Hz, 1H, H20α), 4.18 (d, J=8.7 Hz, 1H,H20β), 4.09 (t, J=6.6 Hz, 2H, butynyl), 3.81 (d, J=7.2 Hz, 1H, H3), 3.36(br s, 1H, 2'OH), 2.55 (m, 1H, H6α), 2.49 (m, 1H, 7OH), 2.44 (m, 2H,butynyl), 2.38 (s, 3H, 4Ac), 2.33 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.96(t, J=2.1 Hz, 1H, butynyl), 1.88 (s, 3H, Me18), 1.83 (m, 1H, H6β), 1.80(s, 1OH), 1.68 (s, 3H, Me19), 1.26 (s, 3H, Me17), 1.15 (s, 3H, Me16).

EXAMPLE 26 ##STR49## Preparation ofN-debenzoyl-N-(n-butoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.087 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(n-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (270mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 154 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(n-butoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 154 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 110 mg (90%) ofN-debenzoyl-N-(n-butoxycarbonyl)taxol, which was recrystallized frommethanol/water.

m.p.150-152° C.; [α]²⁵ _(Na) -62.1° (c 0.0095, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.12 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.32 (m, 8H, aromatic), 6.28 (s, 1H, H10), 6.25 (dd, J=7.7, 7.7 Hz,1H, H13), 5.66 (d, J=7.1 Hz, 1H, H3'), 5.55 (d, J=7.7 Hz, 1H, H2β), 5.30(d, J=8.2 Hz, 1H, NH), 4.93 (dd, J=7.7, 1.7 Hz, 1H, H5), 4.64 (br s, 1H,H2'), 4.40 (m, 1H, H7), 4.29 (d, J=8.2 Hz, 1H, H20α), 4.18 (d, J=8.2 Hz,1H, H20β), 3.95 (m, 2H, butyl), 3.80 (d, J=7.1 Hz, 1H, H3), 3.36 (d,J=4.9 Hz, 1H, 2'OH), 2.53 (m, 1H, H6α), 2.48 (br s, 1H, 7OH), 2.39 (s,3H, 4Ac), 2.31 (m, 2H, H14), 2.23 (s, 3H, 10Ac), 1.87 (m, 1H, H6β), 1.82(br s, 3H, Me18), 1.74 (br s, 1H, 1OH), 1.67 (s, 3H, Me19), 1.48 (m, 2H,butyl), 1.26 (s, 3H, Me17), 1.20 (m, 2H, butyl), 1.14 (s, 3H, Me16),0.82 (t, 3H, Me-butyl).

EXAMPLE 27 ##STR50## Preparation of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (30.0 mg, 0.043 mmol) in0.5 mL of THF at -45° C. was added dropwise 0.047 mL of a 1.0 M solutionof (TMS)₂ NLi in THF. After 0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isobutenylazetidin-2-one(44.2 mg, 0.13 mmol) in 0.4 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% sol2ution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 40.3 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isobutenyl-7-triethylsilyl-N-debenzoyl-N-(t-butoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 40.3 mg (0.038 mmol) of the mixture obtained from theprevious reaction in 2 mL of acetonitrile and 0.1 mL of pyridine at 0°C. was added 0.3 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 34.2 mg of material which was purified by flashchromatography to give 22.4 mg (72%) of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol, whichwas recrystallized from methanol/water.

m.p.147-149° C.; [α]²⁵ _(Na) -65.2° (c 0.0023, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.1 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate para), 7.48 (m, 2H, benzoate meta), 6.45 (s, 1H, NH),6.30 (d, J=8.3 Hz, 1H, H10), 6.18 (dd, J=7.7, 7.7 Hz, 1H, H13), 5.68 (d,J=7.1 Hz, 1H, H2β), 5.31 (m, 1H, vinyl), 5.01 (ddd, J=8.8, 8.8, 3.3 Hz,1H, H3'), 4.95 (d, J=7.7 Hz, 1H, H5), 4.76 (m, 1H, H7), 4.43 (m, 1H,H2'), 4.32 (d, J=7.8 Hz, 1H, H20α), 4.19 (d, J=7.8 Hz, 1H, H20β), 3.81(d, J=7.1 Hz, 1H, H3), 3.74 (d, J=6.6 Hz, 1H, 2'OH), 2.54 (m, 1H, H6α),2.48 (d, J=3.9 Hz, 1H, 7OH), 2.44 (m, 2H, H14), 2.39 (s, 3H, 4Ac), 2.26(s, 3H, Me vinyl), 2.25 (s, 3H, Me vinyl), 2.23 (s, 3H, 10Ac), 1.98 (brs, 3H, Me18), 1.86 (m, 1H, H6β), 1.76 (s, 3H, Me19), 1.43 (s, 9H, 3Met-butoxy) 1.25 (s, 3H, Me17), 1.14 (s, 3H, Me16).

EXAMPLE 28 ##STR51## Preparation ofN-debenzoyl-N-(n-butoxycarbonyl)-3'-desphenyl-3'-isobutenyl taxol

To a solution of 7-triethylsilyl baccatin III (70.0 mg, 0.086 mmol) in0.7 mL of THF at -45° C. was added dropwise 0.10 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(n-butoxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isobutenylazetidin-2-one (94.2 mg, 0.214 mmol) in 0.5 mL of THF was added dropwiseto the mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1.0 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 82.8mg of a mixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-7-triethylsilyl-N-debenzoyl-N-(n-butoxycarbonyl)-3'-desphenyl-3'-isobutenyltaxol and a small amount of the (2'S,3'R)isomer.

To a solution of 82.8 mg (0.083 mmol) of the mixture obtained from theprevious reaction in 6.0 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 67.7 mg of material which was purified by flashchromatography to give 53.2 mg (77%) ofN-debenzoyl-N-(n-butoxycarbonyl)-3'-desphenyl-3'-isobutenyl taxol, whichwas recrystallized from methanol/water.

m.p.132-134° C.; [α]²⁵ _(Na) -64.0° (c 0.0023, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate para), 7.48 (m, 2H, benzoate meta), 6.30 (s, 1H, H10),6.21 (dd, J=7.5, 7.5 Hz, 1H, H13), 5.67 (d, J=7.2 Hz, 1H, H2β), 5.33 (m,1H, olefine of isobutenyl), 4.97 (d, J=7.8, 1H, H5), 4.91 (d, J=8.2 Hz,1H, NH), 4.78 (ddd, J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.43 (m, 1H, H2'),4.31 (d, J=7.8 Hz, 1H, H20α), 4.25 (m, 1H, H7), 4.16 (d, J=7.8 Hz, 1H,H20β), 3.96 (q, J=6.6 Hz, 2H, n-butyloxy), 3.81 (d, J=7.2 Hz, 1H, H3),3.34 (d, J=6.6 Hz, 1H, 2'OH), 2.54 (m, 1H, H6α), 2.50 (d, J=3.9 Hz, 1H,7OH), 2.36 (s, 3H, 4Ac), 2.33 (m, 2H, H14), 2.26 (s, 3H, 10Ac), 2.24 (brs, 3H, Me18), 1.89 (s, 3H, Me19), 1.87 (m, 1H, H6β), 1.77 (s, 3H, Meisobutenyl), 1.75 (s, 1H, 1OH), 1.68 (s, 3H, Me isobutenyl), 1.56 (m,2H, n-butyloxy), 1.32 (m, 2H, n-butyloxy), 1.26 (s, 3H, Me17), 1.15 (s,3H, Me16), 0.85 (t, J=6.6 Hz, 3H, Me of n-butyloxy).

EXAMPLE 29 ##STR52## Preparation of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(isobutyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (40.0 mg, 0.042 mmol) in0.5 mL of THF at -45° C. was added dropwise 0.05 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(isobutyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isobutenylazetidin-2-one(43.0 mg, 0.13 mmol) in 0.5 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 0.5 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 31.2 mg of amixture containing(2'R,3'S)-2'-(2methoxy-2-propoxy)-7-triethylsilyl-3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(isobutyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 31.2 mg (0.030 mmol) of the mixture obtained from theprevious reaction in 2.0 mL of acetonitrile and 0.12 mL of pyridine at0° C. was added 0.25 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 27.7 mg of material which was purified by flashchromatography to give 20.7 mg (83%) of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(isobutyloxycarbonyl)taxol,which was recrystallized from methanol/water.

m.p.147-148° C.; [α]²⁵ _(Na) -58.2° (c 0.0016, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate para), 7.50 (m, 2H, benzoate meta), 6.30 (s, 1H, H10),6.22 (dd, J=7.5, 7.5 Hz, 1H, H13), 5.65 (d, J=7.2 Hz, 1H, H2β), 5.31 (m,1H, olefine of isobuthenyl), 4.95 (d, J=7.8, 1H, H5), 4.91 (d, J=8.2 Hz,1H, NH), 4.76 (ddd, J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.41 (m, 1H, H2'),4.33 (d, J=7.8 Hz, 1H, H20α), 4.25 (m, 1H, H7), 4.16 (d, J=7.8 Hz, 1H,H20β), 3.81 (d, J=7.2 Hz, 1H, H3), 3.71 (dd, J=10.2, 6.6 Hz, 1H,isobuthyl), 3.60 (dd, J=10.2, 6.6 Hz, 1H, isobuthyl), 3.31 (d, J=6.6 Hz,1H, 2'OH), 2.55 (m, 1H, H6α), 2.50 (d, J=3.9 Hz, 1H, 7OH), 2.37 (s, 3H,4Ac), 2.31 (m, 2H, H14), 2.26 (s, 3H, 10Ac), 2.23 (br s, 3H, Me18), 1.89(s, 3H, Me19), 1.87 (m, 1H, H6β), 1.77 (s, 3H, Me isobuthenyl), 1.75 (s,1H, 1OH), 1.66 (s, 3H, Me isobuthenyl), 1.25 (s, 3H, Me17), 1.15 (s, 3H,Me16), 0.76 (d, J=7.2 Hz, 3H, Me of isobuthyl), 0.70 (d, J=6.6 Hz, 3H,Me of isobuthyl).

EXAMPLE 30 ##STR53## Preparation of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(ethoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100.0 mg, 0.142 mmol) in1.0 mL of THF at -45° C. was added dropwise 0.16 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(ethoxycarbonyl)-3-(2'-2"-(2-methoxy-2-propoxy)-4-isobutenylazetidin-2-one(155 mg, 0.43 mmol) in 1.0 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1.0 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 112.2 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isobutenyl-7-triethylsilyl-N-debenzoyl-N-(ethoxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 112.2 mg (0.109 mmol) of the mixture obtained from theprevious reaction in 7.0 mL of acetonitrile and 0.4 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 98.7 mg of material which was purified by flashchromatography to give 81.4 mg (93%) of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(ethoxycarbonyl)taxol, whichwas recrystallized from methanol/water.

m.p.137-140° C.; [α]²⁵ _(Na) -56.2.0° (c 0.0023, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ8.11 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate para), 7.50 (m, 2H, benzoate meta), 6.30 (s, 1H, H10),6.19 (dd, J=7.5, 7.5 Hz, 1H, H13), 5.65 (d, J=7.2 Hz, 1H, H2β), 5.31 (m,1H, olefine of isobuthenyl), 4.98 (d, J=7.8, 1H, H5), 4.90 (d, J=8.2 Hz,1H, NH), 4.75 (ddd, J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.45 (m, 1H, H2'),4.31 (d, J=7.8 Hz, 1H, H20α), 4.25 (m, 1H, H7), 4.16 (d, J=7.8 Hz, 1H,H20β), 3.93 (q, J=7.2 Hz, 2H, ethyl), 3.81 (d, J=7.2 Hz, 1H, H3), 3.34(d, J=6.6 Hz, 1H, 2'OH), 2.54 (m, 1H, H6α), 2.50 (d, J=3.9 Hz, 1H, 7OH),2.36 (s, 3H, 4Ac), 2.33 (m, 2H, H14), 2.26 (s, 3H, 10Ac), 2.24 (br s,3H, Me18), 1.89 (s, 3H, Me19), 1.87 (m, 1H, H6β), 1.78 (s, 3H, Meisobuthenyl), 1.73 (s, 1H, 1OH), 1.68 (s, 3H, Me isobuthenyl), 1.26 (s,3H, Me17), 1.15 (s, 3H, Me16), 1.08 (t, J=7.2 Hz, 3H, Me of ethyl).

EXAMPLE 31 ##STR54## Preparation of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(neopentyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.071 mmol) in0.7 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(neopentyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isobuthenylazetidin-2-one (68.9 mg, 0.21 mmol) in 1.0 mL of THF was added dropwiseto the mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1.0 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 65.1mg of a mixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isobutenyl-7-triethylsilyl-N-debenzoyl-N-(neopentyloxycarbonyl)taxoland a small amount of the (2'S,3'R)isomer.

To a solution of 65.1 mg (0.057 mmol) of the mixture obtained from theprevious reaction in 6.0 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 58.2 mg of material which was purified by flashchromatography to give 31.2 mg (65%) of3'-desphenyl-3'-(isobutenyl)-N-debenzoyl-N-(neopentyloxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p.147-149° C.; [α]²⁵ Na -58.5° (c 0.0019, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.2 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.30(s, 1H,H10), 6.22(dd, J=7.5, 7.5 Hz, 1H, H13), 5.68(d, J=7.2 Hz, 1H, H2β),5.32(m, 1H, olefine of isobuthenyl), 4.98(d, J=7.8, 1H, H5), 4.89(d,J=8.2 Hz, 1H, NH), 4.76(ddd, J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.43(m, 1H,H2'), 4.29(d, J=7.8 Hz, 1H, H20α), 4.25(m, 1H, H7), 4.16(d, J=7.8 Hz,1H, H20β), 3.76(s, 2H, neopenthyloxy), 3.81(d, J=7.2 Hz, 1H, H3),3.34(d, J=6.6 Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.50(d, J=3.9 Hz, 1H,7OH), 2.33(s, 3H, 4Ac), 2.30(m, 2H, H14), 2.26(s, 3H, 10Ac), 2.24(br s,3H, Me18), 1.89(s, 3H, Me19), 1.87(m, 1H, H6β), 1.77(s, 3H, Meisobuthenyl), 1.75(s, 1H, 1OH), 1.68(s, 3H, Me isobuthenyl), 1.26(s, 3H,Me17), 1.20(s, 9H, Me of neopenthyloxy) 1.15(s, 3H, Me16).

EXAMPLE 32 ##STR55## Preparation of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(isopropyloxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.071 mmol) in0.7 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(isopropyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isobutenylazetidin-2-one(56.3 mg, 0.22 mmol) in 1.0 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1.0 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 63.4 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isobutenyl-7-triethylsilyl-N-debenzoyl-N-(isopropyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 63.4 mg (0.057 mmol) of the mixture obtained from theprevious reaction in 5.5 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.66 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 49.2 mg of material which was purified by flashchromatography to give 38.2 mg (82%) of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(isopropyloxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p.145-147° C.; [α]²⁵ Na -58.3° (c 0.0019, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12(d, J=7.2 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.30(s, 1H,H10), 6.20(dd, J=7.5, 7.5 Hz, 1H, H13), 5.65(d, J=7.2 Hz, 1H, H2β),5.31(m, 1H, olefine of isobuthenyl), 4.96(d, J=7.8, 1H, H5), 4.90(d,J=8.2 Hz, 1H, NH), 4.77(ddd, J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.69(m, 1H,isopropyloxy), 4.43(m, 1H, H2'), 4.31(d, J=7.8 Hz, 1H, H20α), 4.24(m,1H, H7), 4.15(d, J=7.8 Hz, 1H, H20β), 3.81(d, J=7.2 Hz, 1H, H3), 3.33(d,J=6.6 Hz, 1H, 2'OH), 2.54(m, 1H, H6α), 2.50(d, J=3.9 Hz, 1H, 7OH),2.34(s, 3H, 4Ac), 2.30(m, 2H, H14), 2.24(s, 3H, 10Ac), 2.21(br s, 3H,Me18), 1.88(s, 3H, Me19), 1.87(m, 1H, H6β), 1.77(s, 3H, Me isobuthenyl),1.75(s, 1H, 1OH), 1.66(s, 3H, Me isobuthenyl), 1.25(s, 3H, Me17),1.16(s, 3H, Me16), 1.14(d, J=6.6 Hz, 3H, Me of isopropyloxy), 1.12(d,J=6.6 Hz, 3H, Me of isopropyloxy).

EXAMPLE 33 ##STR56## Preparation of3'-desphenyl-3-'-isobutenyl-N-debenzoyl-N-(allyloxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.071 mmol) in0.7 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(allyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isobutenylazetidin-2-one(65.4 mg, 0.22 mmol) in 1.0 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1.0 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 64.4 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isobuthenyl-7-triethylsilyl-N-debenzoyl-N-(allyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 64.4 mg (0.058 mmol) of the mixture obtained from theprevious reaction in 6.0 mL of acetonitrile and 0.28 mL of pyridine at0° C. was added 0.7 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 53.2 mg of material which was purified by flashchromatography to give 33.3 mg (71%) of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(allyloxycarbonyl) taxol, whichwas recrystallized from methanol/water.

m.p.137-139° C.; [α]²⁵ Na -59.1° (c 0.0022, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=7.2 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.29(s, 1H,H10), 6.21(dd, J=7.5, 7.5 Hz, 1H, H13), 5.78(m, 1H, allyl), 5.67(d,J=7.2 Hz, 1H, H2β), 5.33(m, 1H, olefine of isobuthenyl), 5.14(m, 2H,allyl), 4.97(d, J=7.8, 1H, H5), 4.91(d, J=8.2 Hz, 1H, NH), 4.78(ddd,J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.43(m, 1H, H2'), 4.31(d, J=7.8 Hz, 1H,H20α), 4.25(m, 1H, H7), 4.18(d, J=7.8 Hz, 1H, H20β), 4.08(d, J=6.6 Hz,2H, allyl) 3.79(d, J=7.2 Hz, 1H, H3), 3.34(d, J=6.6 Hz, 1H, 2'OH),2.55(m, 1H, H6α), 2.50(d, J=3.9 Hz, 1H, 7OH), 2.36(s, 3H, 4Ac), 2.33(m,2H, H14), 2.26(s, 3H, 10Ac), 2.24(br s, 3H, Me18), 1.88(s, 3H, Me19),1.85(m, 1H, H6β), 1.72(s, 3H, Me isobuthenyl), 1.69(s, 1H, 1OH), 1.61(s,3H, Me isobuthenyl), 1.25(s, 3H, Me17), 1.15(s, 3H, Me16).

EXAMPLE 34 ##STR57## Preparation of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(benzoyloxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.071 mmol) in0.7 mL of THF at -4° C. was added dropwise 0.08 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -4° C., a solution ofcis-1-(benzoyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isobutenylazetidin-2-one(63 mg, 0.21 mol) in 0.5 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1.0 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 60.4 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isobutenyl-7-triethylsilyl-N-debenzoyl-N-(benzoyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 60.4 mg (0.053 mmol) of the mixture obtained from theprevious reaction in 5.0 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.65 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 48.2 mg of material which was purified by flashchromatography to give 34.1 mg (74%) of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(benzoyloxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p.148-149° C.; [α]²⁵ Na -53.2.0° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.2 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.48(m, 2H, benzoate meta), 7.22-7.20 (m,3H, benzyl), 7.10-7.05(m, 2H, benzyl), 6.29(s, 1H, H10), 6.21(dd, J=7.5,7.5 Hz, 1H, H13), 5.63(d, J=7.2 Hz, 1H, H2b), 5.33(m, 1H, olefine ofisobuthenyl), 5.06(d, J=12.3 Hz, 1H, benzyl), 4.97(d, J=7.8, 1H, H5),4.91(d, J=8.2 Hz, 1H, NH), 4.85(d, J=12.3 Hz, 1H, benzyl), 4.76(ddd,J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.48(m, 1H, H2'), 4.30(d, J=7.8 Hz, 1H,H20α), 4.25(m, 1H, H7), 4.16(d, J=7.8 Hz, 1H, H20β), 3.81(d, J=7.2 Hz,1H, H3), 3.34(d, J=6.6 Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.49(d, J=3.9Hz, 1H, 7OH), 2.36(s, 3H, 4Ac), 2.32(m, 2H, H14), 2.27(s, 3H, 10Ac),2.24(br s, 3H, Me18), 1.90(s, 3H, Me19), 1.86(m, 1H, H6β), 1.77(s, 3H,Me isobuthenyl), 1.75(s, 1H, 1OH), 1.67(s, 3H, Me isobuthenyl), 1.27(s,3H, Me17), 1.16(s, 3H, Me16).

EXAMPLE 35 ##STR58## Preparation of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(trimethylsilylmethoxycarbonyl)Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.71 mmol) in0.7 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(trimethylsilylmethoxycarbonyl)-3-(2-methoxy-2-propoxy)-4-(isobuthenyl)azetidin-2-one(77.0 mg, 0.22 mmol) in 0.7 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1.0 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 58.4 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isobutenyl-7-triethylsilyl-N-debenzoyl-N-(trimethylsilylmethoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 58.4 mg (0.51 mmol) of the mixture obtained from theprevious reaction in 5.0 mL of acetonitrile and 0.30 mL of pyridine at0° C. was added 0.60 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 51.2 mg of material which was purified by flashchromatography to give 31.1 mg (71%) of3'-desphenyl-3'-isobutenyl-N-debenzoyl-N-(trimethylsilylmethoxycarbonyl)taxol, which was recrystallized from methanol/water.

m.p.149-151° C.; [α]²⁵ Na -58.0° (c 0.0018, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=7.2 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.48(m, 2H, benzoate meta), 6.30(s, 1H,H10), 6.21(dd, J=7.5, 7.5 Hz, 1H, H13), 5.67(d, J=7.2 Hz, 1H, H2β),5.33(m, 1H, olefine of isobuthenyl), 4.97(d, J=7.8, 1H, H5), 4.88(d,J=8.2 Hz, 1H, NH), 4.76(ddd, J=8.7, 8.7, 2.7 Hz, 1H, H3'), 4.41(m, 1H,H2'), 4.28(d, J=7.8 Hz, 1H, H20α), 4.25(m, 1H, H7), 4.16(d, J=7.8 Hz,1H, H20β), 3.76(d, J=7.2 Hz, 1H, H3), 3.68(d, J=14.1 Hz, 1H, CH₂ TMS),3.51(d, J=14.1 Hz, 1H, CH₂ TMS), 3.41(d, J=6.6 Hz, 1H, 2'OH), 2.55(m,1H, H6α), 2.50(d, J=3.9 Hz, 1H, 7OH), 2.29(s, 3H, 4Ac), 2.25(m, 2H,H14), 2.21(s, 3H, 10Ac), 2.24(br s, 3H, Me18), 1.89(s, 3H, Me19),1.87(m, 1H, H6β), 1.77(s, 3H, Me isobuthenyl), 1.75(s, 1H, 1OH), 1.68(s,3H, Me isobuthenyl), 1.18(s, 3H, Me17), 1.15(s, 3H, Me16), -0.04(s, 9H,Me₃ Si--).

EXAMPLE 36 ##STR59## Preparation of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9.beta.-hydroxy-10-desacetylTaxol

To a solution of7,10-(bis)-O-triethylsilyl-9-desoxo-9β-hydroxy-10-deacetyl baccatin(III) (70.0 mg, 0.09 mmol) in 1.0 mL of THF at -45° C. was addeddropwise 0.10 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-(2-methoxyisopropyloxy)-4-(isobutenyl)azetidin-2-one(84.5 mg, 0.27 mmol) in 1.0 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 88.3 mg of amixture containing(2'R,3'S)-2',7,10-(tris)-O-triethylsilyl-3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9β-hydroxy-10-desacetyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 88.3 mg (0.080 mmol) of the mixture obtained from theprevious reaction in 13.5 mL of acetonitrile and 0.55 mL of pyridine at0° C. was added 1.90 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 67.2 mg of material which was purified by flashchromatography to give 52.7 mg (82%) of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9.beta.-hydroxy-10-desacetyltaxol, which was recrystallized from methanol/water.

m.p.138-140° C.; [α]²⁵ Na -55.2° (c 0.0026, CHCl₃).

¹ H NMR (MeOH, 300 MHz) δ 8.11(d, J=7.1 Hz, 2H, benzoate ortho), 7.61(m,1H, benzoate para), 7.48(m, 2H, benzoate meta), 6.13(m, 1H, H13),6.12(m, 1H, H2), 5.21(br s., 1H, H3'), 5.02(d, J=5.3 Hz, 1H, H10),4.93(d, J=8.1 Hz, 1H, H5), 4.85(d, J=9.1 hz, 1H, NH), 4.84(d, J=8.5 Hz,1H, Me₂ C═CH--), 4.50(br s, 1H, H2'), 4.50(d, J=5.5 Hz, 1H, H9), 4.22(d,J=8.1, 1H, H20α), 4.18(d, J=8.1 Hz, 1H, H20β), 3.89(dd, J=9.4, 7.5 Hz,1H, H7), 3.12(d, J=5.5 Hz, H3), 2.45(m, 1H, H6α), 2.31(m, 1H, H14α),2.29(s, 3H, 4Ac), 2.18(m, 1H, H14β), 1.85(ddd, J=15.1, 9.4, 1.2 Hz,H6β), 1.81(s, 3H, Me16), 1.76(s, 3H, Me18), 1.72(s, 6H, 2Me fromisobuthenyl), 1.61(s, 3H, Me19), 1.39(s, 9H, 3Me t-buthoxy), 1.26(s, 3H,Me17).

EXAMPLE 37 ##STR60## Preparation of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxyTaxol

To a solution of 7-O-triethylsilyl-10-desacetoxy baccatin (III) (50.0mg, 0.077 mmol) in 0.8 mL of THF at -45° C. was added dropwise 0.09 mLof a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-(2-methoxyisopropyloxy)-4-(isobutenyl)azetidin-2-one(58.0 mg, 0.193 mmol) in 0.7 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 62.7 mg of amixture containing(2'R,3'S)-2'-O-(2-methoxyisopropyl)-7-O-triethylsilyl-3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 62.7 mg (0.059 mmol) of the mixture obtained from theprevious reaction in 3.5 mL of acetonitrile and 0.16 mL of pyridine at0° C. was added 0.55 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 51.5 mg of material which was purified by flashchromatography to give 43.0 mg (95%) of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxytaxol, which was recrystallized from methanol/water.

m.p.153-155° C.; [α]²⁵ Na -56.3° (c 0.003, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.10(d, J=7.3 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.47(m, 2H, benzoate meta), 6.15(td, J=8.5,1.8 Hz, 1H, H13), 5.69(d, J=6.9 Hz, 1H, H2), 5.32(d, J=9.2 Hz, 1H, NH),4.93(dd, J=9.6, 1.8 Hz, 1H, H5), 4.82(d, J=8.7 Hz, 1H, Me₂ C═CH--),4.76(td, J=8.7, 2.7 Hz, 1H, H3'), 4.37(d, J=8.7 Hz, 1H, H20α), 4.22(d,J=8.7 Hz, 1H, H20β), 4.18(d, J=2.7 Hz, 1H, H2'), 4.03(d, J=7.3 Hz, 1H,H7), 3.82(d, J=15.2 Hz, 1H, H10α), 3.47(m, 1H, 2'OH), 3.41(d, J=6.6 Hz,1H, H3), 2.60(m, 1H, H6α), 2.39(m, 1H, H10β), 2.37(s, 3H, 4Ac), 2.18(s,1H, 7 OH), 2.08(m, 1H, H14α),1.78(m, 1H, H14β), 1.76(s, 3H, Me18),1.74(s, 6H, 2Me from isobuthenyl), 1.63(m, 1H, H6β), 1.36(s, 9H, 3Met-buthoxy) 1.26(s, 3H, Me17), 1.18(s, 3H, Me19), 1.15(s, 3H, Me16).

EXAMPLE 38 ##STR61## Preparation of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-ketoTaxol

To a solution of 7-O-triethylsilyl-9-desoxo-10-desacetoxy-10-ketobaccatin (III) (30.0 mg, 0.047 mmol) in 0.5 mL of THF at -45° C. wasadded dropwise 0.05 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane.After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-(2-methoxyisopropyloxy)-4-(isobutenyl)azetidin-2-one (44.1 mg, 0.141 mmol) in 0.5 mL of THF was added dropwiseto the mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 40.8mg of a mixture containing(2'R,3'S)-2'-O-(2-methoxyisopropyl)-7-O-triethylsilyl-3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-ketotaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 40.8 mg (0.043 mmol) of the mixture obtained from theprevious reaction in 4 mL of acetonitrile and 0.2 mL of pyridine at 0°C. was added 0.5 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 34.4 mg of material which was purified by flashchromatography to give 23.0 mg (70%) of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-ketotaxol, which was recrystallized from methanol/water.

m.p.149-153° C.; [α]²⁵ Na -56.3° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12(d, J=7.2 Hz, 2H, benzoate ortho),7.64(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 6.12(t, J=7.5Hz, 1H, H13), 5.95(d, J=6.2 Hz, 1H, H2), 5.30(d, J=8.9 Hz, 1H, NH),4.94(d, J=8.2 Hz, 1H, H5), 4.88(d, J=8.9 Hz, 1H, Me₂ C═CH--), 4.79(td,J=8.9, 2.4 Hz, 1H, H3'), 4.34(d, J=8.2 Hz, 1H, H20α), 4.27(dd, J=5.5,2.7 Hz, 1H, H2'), 4.19(d, J=8.2 Hz, 1H, H20β),, 3.73(m, 1H, H7), 3.67(brs, 1H, 2'OH), 3.13(d, J=5.1 Hz, 1H, H3), 3.12(d, J=15.7 Hz, 1H, H9α),2.90(d, J=15.7 Hz, 1H, H9β), 2.55(m, 1H, H6α), 2.47(m, 1H, H14β),2.32(s, 3H, 4Ac), 2.28(m, 1H, H14α), 2.04(br s, 1H, 7 OH), 1.88(s, 1H, 1OH), 1.82(m, 1H, H6β), 1.79(s, 3H, Me18), 1.76(s, 6H, 2Me fromisobuthenyl), 1.57(s, 3H, Me16), 1.47 (s, 3H, Me19), 1.40(s, 9H, 3Met-buthoxy) 1.30(s, 3H, Me17).

EXAMPLE 39 ##STR62## Preparation of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-O-acetyl-10-desacetylTaxol

To a solution of7-O-triethylsilyl-9-desoxy-9b-acetoxy-10-desacetoxy-10-keto baccatin(III) (33.0 mg, 0.047 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.05 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-t-buthoxycarbonyl-3-(2-methoxyisopropyloxy)-4-isobutenylazetidin-2-one(44.1 mg, 0.141 mmol) in 0.5 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 41.9 mg of amixture containing(2'R,3'S)-2'-O-(2-methoxyisopropyl)-7-O-triethylsilyl-3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxy-9β-acetoxy-10-desacetoxy-10-ketotaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 41.9 mg (0.045 mmol) of the mixture obtained from theprevious reaction in 3.5 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.50 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 32.4 mg of material which was stirred with 1.0 gof silica gel in 5 mL of methylene chloride at room temperature in 48hrs. The organic layer was purified by filtration through silica gel togive 26.2 mg (70%) of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-O-acetyl-10-desacetyltaxol.

m.p.1136-139° C.; [α]²⁵ Na -60.2° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.10(d, J=7.3 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.48(m, 2H, benzoate meta), 6.16(td, J=8.7,1.8 Hz, 1H, H13), 5.68(d, J=6.9 Hz, 1H, H2), 5.48(dd, J=10.5, 7.3 Hz,1H, H7), 5.33(d, J=1.8 Hz, 1H, H10), 5.32(d, J=9.2 Hz, 1H, NH), 4.94(dd,J=9.6, 1.8 Hz, 1H, H5), 4.80(d, J=8.7 Hz, 1H, Me₂ C═CH--), 4.75(td,J=8.7, 2.7 Hz, 1H, H3'), 4.33(d, J=8.7 Hz, 1H, H20α), 4.23(d, J=2.7 Hz,1H, H2'), 4.22(d, J=8.7 Hz, 1H, H20β), 4.01(d, J=6.9 Hz, 1H, H3),3.98(d, J=1.8 Hz, 1H, 10OH), 3.68(m, 1H, 2'OH), 2.54(m, 1H, H6α),2.37(s, 3H, 4Ac), 2.35(m, 1H, H14α), 2.01(m, 1H, H14β), 1.99(s, 3H,7Ac), 1.98(br s, 3H, Me18), 1.93(m, 1H, H6β), 1.85(s, 3H, Me19), 1.77(s,6H, 2Me from isobuthenyl), 1.61(s, 1H, 7OH), 1.37(s, 9H, 3Me t-buthoxy),1.23(s, 3H, Me17), 1.10(s, 3H, Me16).

EXAMPLE 40 ##STR63## Preparation of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxyTaxol

To a solution of 7-deshydroxy baccatin (III) (38.7 mg, 0.063 mmol) in0.8 mL of THF at -45° C. was added dropwise 0.08 mL of a 0.98 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-(2-methoxyisopropyloxy)-4-(isobutenyl)azetidin-2-one(59.0 mg, 0.19 mmol) in 0.8 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 43.4 mg of amixture containing(2'R,3'S)-2'-O-(2-methoxyisopropyl)-3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 43.4 mg (0.049 mmol) of the mixture obtained from theprevious reaction in 3.5 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.5 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 40.2 mg of material which was purified by flashchromatography to give 34.1 mg (86%) of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxytaxol, which was recrystallized from methanol/water.

m.p.142-144° C.; [α]²⁵ Na -53.3° (c 0.0024, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=7.3 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.47(m, 2H, benzoate meta), 6.41(s, 1H,H10), 6.20(dd, J=9.0, 0.9 Hz, 1H, H13), 5.67(d, J=7.2 Hz, 1H, H2),5.39(d, J=6.9 Hz, 1H, NH), 5.32(d, J=9.0 Hz, 1H, H3'), 4.93(dd, J=8.7,2.1 Hz, 1H, H5), 4.81(d, J=8.7 Hz, 1H, Me₂ C═CH--), 4.61(d, J=3.3 Hz,1H, H2'), 4.30(d, J=8.1 Hz, 1H, H20α), 4.17(d, J=8.1 Hz, 1H, H20β),3.75(d, J=6.6 Hz, 1H, H3), 3.41(m, 1H, 2'OH), 2.36(s, 3H, 4Ac), 2.33(m,1H, H14α), 2.30(m, 1H, H14β), 2.26(m, 1H, H6α), 2.08(m, 1H, H7α),1.94(m, 1H, H6β), 1.85(br s, 3H, Me18), 1.73(s, 6H, 2Me fromisobuthenyl), 1.70(s, 3H, Me19), 1.66(s, 1H, 1 OH), 1.53(m, 1H, H7β),1.41(s, 9H, 3Me t-buthoxy), 1.25(s, 3H, Me16), 1.15(s, 3H, Me17).

EXAMPLE 41 ##STR64## Preparation of3'-desphenyl-3'-(isobutenyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxyTaxol

To a solution of 7-deshydroxy-10-desacetoxy baccatin (III) (28.7 mg,0.051 mmol) in 0.7 mL of THF at -45° C. was added dropwise 0.06 mL of a0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-(2-methoxyisopropyloxy)-4-(isobutenyl)azetidin-2-one(47.3 mg, 0.15 mmol) in 0.7 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 40.3 mg of amixture containing(2'R,3'S)-2'-O-(2-methoxyisopropyl)-3'-desphenyl-3'-(isobutenyl)-N-debenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 40.3 mg (0.046 mmol) of the mixture obtained from theprevious reaction in 3.2 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.47 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 35.2 mg of material which was purified by flashchromatography to give 24.0 mg (70%) of3'-desphenyl-3'-(isobutenyl)-N-debenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxytaxol, which was recrystallized from methanol/water.

m.p.122-125° C.; [α]²⁵ Na -64.3° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12(d, J=7.1 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.48(m, 2H, benzoate meta), 6.11(td, J=8.1,1.8 Hz, 1H, H13), 5.68(d, J=6.9 Hz, 1H, H2), 5.23(d, J=9.9 Hz, 1H, NH),5.12(d, J=9.9 Hz, 1H, H3'), 4.96(dd, J=9.1, 2.7 Hz, 1H, H5), 4.80(d,J=8.7 Hz, 1H, Me₂ C═CH--), 4.58(dd, J=5.7, 2.1 Hz, 1H, H2'), 4.30(d,J=8.1, 1H, H20α), 4.19(d, J=8.1 Hz, 1H, H20β), 3.97(d, J=6.9 Hz, H3),3.83(d, J=16.5, 1H, H10α), 3.33(m, 1H, H10β), 3.30(m, 1H, 2'OH), 2.39(m,1H, H14α), 2.35(s, 3H, 4Ac), 2.26(m, 1H, H14β), 2.19(m, 1H, H6α),2.10(m, 1H, H7α), 1.95(m, 1H, H6β), 1.73(s, 3H, Me18), 1.69(s, 6H, 2Mefrom isobuthenyl), 1.63(s, 3H, Me19), 1.44(m, 1H, H7β), 1.39(br. s, 1H,1 OH), 1.35(s, 9H, 3Me t-buthoxy), 1.25(s, 3H, Me16), 1.15(s, 3H, Me17).

EXAMPLE 42 ##STR65## Preparation of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxyTaxol

To a solution of 7-O-triethylsilyl-10-desacetoxy baccatin (III) (47.5mg, 0.073 mmol) in 0.7 mL of THF at -45° C. was added dropwise 0.08 mLof a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-thienyl)-azetidin-2-one(70.0 mg, 0.182 mmol) in 0.7 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 64.3 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 64.3 mg (0.056 mmol) of the mixture obtained from theprevious reaction in 3.2 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.50 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 46.3 mg of material which was purified by flashchromatography to give 40.1 mg (91%) of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxytaxol, which was recrystallized from methanol/water.

m.p.158-160° C.; [α]²⁵ Na -58.4° (c 0.0028, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=6.9 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 7.27(dd, J=5.5,1.2 Hz, 1H, thienyl), 7.06(d, J=3.3 Hz, 1H, thienyl), 7.01(dd, J=5.7,3.9 Hz, 1H, thienyl), 6.13(td, J=6.3, 0.9 Hz, 1H, H13), 5.70(d, J=6.9Hz, 1H, H2), 5.49(d, J=9.2 Hz, 1H, NH), 5.34(d, J=9.9 Hz, 1H, H3'),4.62(dd, J=5.4 2.1 Hz, 1H, H5), 4.30(d, J=8.1 Hz, 1H, H20α), 4.29(s, 1H,H2'), 4.17(d, J=8.1 Hz, 1H, H20β), 4.06(d, J=6.9 Hz, 1H, H7), 3.81(d,J=15.3 Hz, H10α),3.51(d, J=6.6 Hz, 1H, H3), 3.41(m, 1H, 2'OH), 2.61(m,1H, H6α), 2.36(s, 3H, 4Ac), 2.30(m, 1H, H10β), 2.17(br s, 1H, 7 OH),2.06(m, 1H, H14α), 1.81(m, 1H, H14β), 1.76(br s, 3H, Me18), 1.66(s, 1H,1 OH), 1.62(m, 1H, H6β), 1.35(s, 9H, 3Me t-buthoxy), 1.25(s, 3H, Me17),1.19(s, 3H, Me19), 1.17(s, 3H, Me16).

EXAMPLE 43 ##STR66## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxy Taxol

To a solution of 7-O-triethylsilyl-10-desacetoxy baccatin (III) (50.0mg, 0.077 mmol) in 0.8 mL of THF at -45° C. was added dropwise 0.09 mLof a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-triethylsiloxy-4-phenylazetidin-2-one (67.5 mg,0.193 mmol) in 0.8 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and 2 kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 72.0 mg of amixture containing (2'R, 3'S)-2',7-(bis)-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 72.0 mg (0.071 mmol) of the mixture obtained from theprevious reaction in 3.8 mL of acetonitrile and 0.17 mL of pyridine at0° C. was added 0.60 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 57.4 mg of material which was purified by flashchromatography to give 39.4 mg (71%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-10-desactoxy taxol, which wasrecrystallized from methanol/water.

m.p.145-147° C.; [α]²⁵ Na -54.4° (c 0.0027, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=7.1 Hz, 2H, benzoate ortho),7.61-7.23(m, 8H, benzoate, phenyl), 6.13(td, J=6.3, 0.9 Hz, 1H, H13),5.68(d, J=6.9 Hz, 1H, H2), 5.43(d, J=9.2 Hz, 1H, NH), 5.26(d, J=9.9 Hz,1H, H3'), 4.96(dd, J=5.4 2.1 Hz, 1H, H5), 4.31(d, J=8.1 Hz, 1H, H20α),4.22(s, 1H, H2'), 4.18(d, J=8.1 Hz, 1H, H20β), 4.03(d, J=6.9 Hz, 1H,H7), 3.81(d, J=15.1 Hz, H10α),3.43(m, 1H, 2'OH), 3.40(d, J=6.6 Hz, 1H,H3), 2.60(m, 1H, H6α), 2.38(s, 3H, 4Ac), 2.32(m, 1H, H10β), 2.15(br s,1H, 7 OH), 2.09(m, 1H, H14α), 1.83(m, 1H, H14β), 1.78(br s, 3H, Me18),1.66(s, 1H, 1 OH), 1.63(m, 1H, H6β), 1.36(s, 9H, 3Me t-butoxy), 1.25(s,3H, Me17), 1.18(s, 3H, Me19), 1.16(s, 3H, Me16).

EXAMPLE 44 ##STR67## Preparation of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxyTaxol

To a solution of 7-O-triethylsilyl-10-desacetoxy baccatin (III) (50.0mg, 0.077 mmol) in 0.8 mL of THF at -45° C. was added dropwise 0.09 mLof a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-triethylsiloxy-4-(2-furyl)azetidin-2-one (72.8mg, 0.195 mmol) in 0.8 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 69.4 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 69.4 mg (0.068 mmol) of the mixture obtained from theprevious reaction in 3.8 mL of acetonitrile and 0.17 mL of pyridine at0° C. was added 0.60 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 59.0 mg of material which was purified by flashchromatography to give 41.0 mg (76%) of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-10-desacetoxytaxol, which was recrystallized from methanol/water.

m.p.151-153° C.; [α]²⁵ Na -56.5° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=7.3 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.49(m, 2H, benzoate meta), 7.41(m, 1H,furyl), 6.37(m, 1H, furyl), 6.34(m, 1H, furyl), 6.13(dd, J=6.3, 0.9 Hz,1H, H13), 5.69(d, J=6.6 Hz, 1H, H2), 5.49(d, J=9.2 Hz, 1H, NH), 5.34(d,J=9.9 Hz, 1H, H3'), 4.62(dd, J=5.4, 2.1 Hz, 1H, H5), 4.30(d, J=8.1 Hz,1H, H20α), 4.29(s, 1H, H2'), 4.17(d, J=8.1 Hz, 1H, H20β), 4.06(d, J=6.9,1H, H7), 3.81(d, J=15.3 Hz, 1H, H10α), 3.51(d, J=6.6 Hz, 1H, H3),3.41(m, 1H, 2'OH), 2.61(m, 1H, H6α), 2.36(s, 3H, 4Ac), 2.32(m, 2H,H14α), 2.28(m, 1H, H10β), 2.17(br s, 1H, 7OH), 2.14(m, 1H, H14α),1.82(m, 1H, H14β), 1.76(br s, 3H, Me18), 1.66(s, 1H, 1 OH), 1.62(m, 1H,H6β), 1.35(s, 9H, 3Me t-butoxy), 1.25(s, 3H, Me17), 1.19(s, 3H, Me19),1.16(s, 3H, Me16).

EXAMPLE 45 ##STR68## Preparation of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-ketoTaxol

To a solution of 7-O-triethylsilyl-9-desoxo-10-desacetoxy-10-ketobaccatin (III) (25.0 mg, 0.039 mmol) in 0.5 mL of THF at -45° C. wasadded dropwise 0.05 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane.After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(45.0 mg, 0.117 mmol) in 0.5 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 36.2 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-ketotaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 36.2 mg (0.035 mmol) of the mixture obtained from theprevious reaction in 3.0 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.45 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 29.4 mg of material which was purified by flashchromatography to give 24.3 mg (87%) of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-ketotaxol, which was recrystallized from methanol/water.

m.p.163-169° C.; [α]²⁵ Na -54.2° (c 0.0023, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12(d, J=7.3 Hz, 2H, benzoate ortho),7.64(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 7.26(m, 1H,thienyl), 7.10(d, J=3.4 Hz, 1H, thienyl), 6.99(dd, J=5.1, 3.4 Hz, 1H,thienyl), 6.12(td, J=6.1, 1.0 Hz, 1H, H13), 5.95(d, J=5.9 Hz, 1H, H2),5.50(d, J=4.4 Hz, 1H, NH), 5.42(d, J=9.8 Hz, 1H, H3'), 4.94(d, J=8.3 Hz,1H, H5), 4.64(dd, J=4.2, 2.0 Hz, 1H, 2'), 4.33(d, J=7.8 Hz, 1H, H20α),4.18(d, J=7.8 Hz, 1H, H20β), 3.90(br s, 1H, 2'OH), 3.73(m, 1H, H7),3.11(d, J=15.8 Hz, H9α), 3.09(d, J=5.1 Hz, 1H, H3), 2.90(d, J=15.6 Hz,1H, H9β), 2.54(m, 1H, H6α), 2.45(m, 1H, H14β), 2.31(s, 3H, 4Ac), 2.28(m,1H, H14α), 2.01(br s, 1H, 7 OH), 1.88(s, 1H, 1 OH), 1.83(m, 1H, H6β),1.69(s, 3H, Me18), 1.56(s, 3H, Me16), 1.46(s, 3H, Me19), 1.40(s, 9H, 3Met-buthoxy), 1.29(s, 3H, Me17).

EXAMPLE 46 ##STR69## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-keto Taxol

To a solution of 7-O-triethylsilyl-9-desoxo-10-desacetoxy-10-ketobaccatin (III) (30.0 mg, 0.047 mmol) in 0.5 mL of THF at -45° C. wasadded dropwise 0.05 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane.After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-phenylazetidin-2-one (53.1mg, 0.14 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 43.7 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-ketotaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 43.7 mg (0.042 mmol) of the mixture obtained from theprevious reaction in 4.0 mL of acetonitrile and 0.20 mL of pyridine at0° C. was added 0.50 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 33.2 mg of material which was purified by flashchromatography to give 24.1 mg (73%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-10-desacetoxy-10-keto taxol,which was recrystallized from methanol/water.

m.p.162-165° C.; [α]²⁵ Na -58.7° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=7.1 Hz, 2H, benzoate ortho),7.63(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 7.40-7.29(m, 5H,benzoate, phenyl), 6.11(td, J=7.8, 1.0 Hz, 1H, H13), 5.94(d, J=6.4 Hz,1H, H2), 5.52(d, J=9.8 Hz, 1H, H3'), 5.27(d, J=9.3 Hz, 1H, NH), 4.93(dd,J=8.8 Hz, 1H, H5), 4.64(br s, 1H, H2'), 4.32(d, J=8.3 Hz, 1H, H20α),4.18(d, J=8.3 Hz, 1H, H20β), 3.88(br s, 1H, 2'OH), 3.71(m, 1H, H7),3.11(d, J=5.1 Hz, 1H, H3), 3.10(d, J=15.7 Hz, H9α), 2.88(d, J=16.1, 1H,H9β), 2.54(m, 1H, H6α), 2.44(m, 1H, H14β), 2.29(s, 3H, 4Ac), 2.26(m, 1H,H14α), 2.02(br s, 1H, 7 OH), 1.88(s, 1H, 1 OH), 1.80(m, 1H, H6β),1.65(s, 3H, Me18), 1.55(s, 3H, Me16), 1.46(s, 3H, Me19), 1.35(s, 9H, 3Met-butoxy), 1.29(s, 3H, Me17).

EXAMPLE 47 ##STR70## Preparation of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxyTaxol

To a solution of 7-deshydroxy-10-desacetoxy baccatin (III) (25.0 mg,0.044 mmol) in 0.7 mL of THF at -45° C. was added dropwise 0.05 mL of a0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-thienyl)-azetidin-2-one(50.0 mg, 0.13 mmol) in 0.7 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 35.4 mg of amixture containing(2'R,3'S)-2'-O-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 35.4 mg (0.037 mmol) of the mixture obtained from theprevious reaction in 3.2 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.47 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 32.4 mg of material which was purified by flashchromatography to give 20.5 mg (71%) of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxytaxol, which was recrystallized from methanol/water.

m.p.132-134° C.; [α]²⁵ Na -61.3° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.14(d, J=7.1 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 7.29(dd, J=5.4,1.2 Hz, 1H, thienyl), 7.09(d, J=3.3 Hz, 1H, thienyl), 7.01(dd, J=5.4,3.3 Hz, 1H, thienyl), 6.14(td, J=8.4, 1.8 Hz, 1H, H13), 5.69(d, J=6.9Hz, 1H, H2), 5.24(d, J=9.9 Hz, 1H, NH), 5.19(d, J=9.9 Hz, 1H, H3'),4.93(dd, J=9.3, 2.7 Hz, 1H, H5), 4.62(dd, J=5.7, 2.1 Hz, 1H, H2'),4.31(d, J=8.1, 1H, H20α), 4.21(d, J=8.1 Hz, 1H, H20β), 3.98(d, J=6.9 Hz,H3), 3.84(d, J=16.5, 1H, H10α), 3.38(m, 1H, H10β), 3.33(m, 1H, 2'OH),2.40(m, 1H, H14α), 2.37(s, 3H, 4Ac), 2.27(m, 1H, H14β), 2.20(m, 1H,H6α), 2.11(m, 1H, H7α), 1.95(m, 1H, H6β), 1.74(s, 3H, Me18), 1.71(s, 3H,Me19), 1.46(m, 1H, H7β), 1.40(br. s, 1H, 1 OH), 1.34(s, 9H, 3Met-buthoxy), 1.24(s, 3H, Me16), 1.13(s, 3H, Me17).

EXAMPLE 48 ##STR71## Preparation of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxyTaxol

To a solution of 7-deshydroxy-10-desacetoxy baccatin (III) (35.0 mg,0.061 mmol) in 0.8 mL of THF at -45° C. was added dropwise 0.07 mL of a0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-furyl)-azetidin-2-one(68.0 mg, 0.18 mmol) in 0.7 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 56.3 mg of amixture containing(2'R,3'S)-2'-O-triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 56.3 mg (0.06 mmol) of the mixture obtained from theprevious reaction in 4.6 mL of acetonitrile and 0.22 mL of pyridine at0° C. was added 0.68 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 48.3 mg of material which was purified by flashchromatography to give 31.7 mg (69%) of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxytaxol, which was recrystallized from methanol/water.

m.p.128-131° C.; [α]²⁵ Na -66.9° (c 0.0028, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=6.9 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.48(m, 2H, benzoate meta), 7.40(m, 1H,furyl), 6.38(m, 1H, furyl), 6.32(m, 1H, furyl), 6.12(td, J=8.1, 1.8 Hz,1H, H13), 5.67(d, J=6.9 Hz, 1H, H2), 5.22(d, J=9.9 Hz, 1H, NH), 5.17(d,J=9.9 Hz, 1H, H3'), 4.91(dd, J=9.1, 2.7 Hz, 1H, H5), 4.60(dd, J=5.7, 2.1Hz, 1H, H2'), 4.28(d, J=8.1, 1H, H20α), 4.21(d, J=8.1 Hz, 1H, H20β),3.95(d, J=6.9 Hz, H3), 3.82(d, J=16.5, 1H, H10α), 3.33(m, 1H, H10β),3.31(m, 1H, 2'OH), 2.38(m, 1H, H14α), 2.35(s, 3H, 4Ac), 2.23(m, 1H,H14β), 2.20(m, 1H, H6α), 2.11(m, 1H, H7α), 1.94(m, 1H, H6β), 1.73(s, 3H,Me18), 1.71(s, 3H, Me19), 1.43(m, 1H, H7β), 1.38(br. s, 1H, 1 OH),1.32(s, 9H, 3Me t-buthoxy), 1.23(s, 3H, Me16), 1.12(s, 3H, Me17).

EXAMPLE 49 ##STR72## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxy Taxol

To a solution of 7-deshydroxy-10-desacetoxy baccatin (III) (28.0 mg,0.049 mmol) in 0.7 mL of THF at -45° C. was added dropwise 0.06 mL of a0.98 M solution of LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., asolution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(phenyl)azetidin-2-one (56.0mg, 0.15 mmol) in 0.7 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 38.4 mg of amixture containing(2'R,3'S)-2'-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 38.4 mg (0.041 mmol) of the mixture obtained from theprevious reaction in 3.2 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.46 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 33.8 mg of material which was purified by flashchromatography to give 27.4 mg (71%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy-10-desacetoxy taxol,which was recrystallized from methanol/water.

m.p.135-138° C.; [α]²⁵ Na -65.2° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12(d, J=7.1 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 7.42-7.29(m, 5H,phenyl), 6.12(td, J=8.1, 1.8 Hz, 1H, H13), 5.66(d, J=6.9 Hz, 1H, H2),5.21(d, J=9.9 Hz, 1H, NH), 5.16(d, J=9.9 Hz, 1H, H3'), 4.92(dd, J=9.1,2.7 Hz, 1H, H5), 4.58(dd, J=5.7, 2.1 Hz, 1H, H2'), 4.30(d, J=8.1, 1H,H20α), 4.21(d, J=8.1 Hz, 1H, H20β), 3.97(d, J=6.9 Hz, H3),3.82(d,J=16.5, 1H, H10α), 3.41(m, 1H, H10β), 3.36(m, 1H, 2'OH), 2.40(m, 1H,H14α), 2.38(s, 3H, 4Ac), 2.26(m, 1H, H14β), 2.20(m, 1H, H6α), 2.13(m,1H, H7α), 1.93(m, 1H, H6β), 1.73(s, 3H, Me18), 1.70(s, 3H, Me19),1.43(m, 1H, H7β), 1.38(br. s, 1H, 1 OH), 1.32(s, 9H, 3Me t-buthoxy),1.25(s, 3H, Me16), 1.15(s, 3H, Me17).

EXAMPLE 50 ##STR73## Preparation of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-O-acetyl-10-desacetylTaxol

To a solution of7-O-triethylsilyl-9-desoxy-9β-acetoxy-10-desacetoxy-10-keto baccatin(III) (33.2 mg, 0.047 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.05 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(54.2 mg, 0.141 mmol) in 0.5 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 46.5 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-buthoxycarbonyl)-9-desoxy-9β-acetoxy-10-desacetoxy-10-ketotaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 46.5 mg (0.043 mmol) of the mixture obtained from theprevious reaction in 3.5 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.50 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 32.7 mg of material which was purified by flashchromatography to give 22.2 mg (61%) of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-O-acetyl-10-desacetyltaxol, which was recrystallized from methanol/water.

m.p.140.5-143° C.; [α]²⁵ Na -58.6° (c 0.00245, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=6.9 Hz, 2H, benzoate ortho),7.62(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 7.29(dd, J=5.5,1.4 Hz, 1H, thienyl), 7.09(d, J=3.2 Hz, 1H, thienyl), 7.01(dd, J=3.7,1.4 Hz, 1H, thienyl), 6.22(dd, J=8.3, 0.9 Hz, 1H, H13), 5.68(d, J=6.9Hz, 1H, H2), 5.51(d, J=8.7 Hz, H7), 5.45(dd, J=10.5, 7.3 Hz, 1H, H3'),5.33(d, J=9.2 Hz, 1H, NH), 5.32(s, 1H, H10), 4.93 (dd, J=9.6 1.8 Hz, 1H,H5), 4.64(s, 1H, H2'), 4.33(d, J=8.7 Hz, 1H, H20α), 4.23(d, J=8.7 Hz,1H, H20β), 4.01(d, J=1.8 Hz, 1H, 10 OH), 4.00(d, J=6.9 Hz, 1H, H3),3.46(m, 1H, 2'OH), 2.54(m, 1H, H6α), 2.39(s, 3H, 4Ac), 2.33(m, 2H,H14α), 2.01(m, 1H, H14β), 1.99(s, 3H, 7 Ac), 1.92(br s, 3H, Me18),1.90(m, 1H, H6β), 1.70(s, 3H, Me19), 1.53(s, 1H, 1 OH), 1.35(s, 9H, 3Met-buthoxy) 1.23(s, 3H, Me17), 1.10(s, 3H, Me16).

EXAMPLE 51 ##STR74## Preparation of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-O-acetyl-10-desacetylTaxol

To a solution of7-O-triethylsilyl-9-desoxy-9β-acetoxy-10-desacetoxy-10-keto baccatin(III) (33.0 mg, 0.047 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.05 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(52.0 mg, 0.141 mmol) in 0.5 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 42.1 mg of amixture containing(2'R,3'S)-2'7-(bis)-O-triethylsilyl-9-desoxy-9β-acetoxy-10-desacetoxy-10-ketobaccatin (III) and a small amount of the (2'S,3'R) isomer.

To a solution of 42.1 mg (0.045 mmol) of the mixture obtained from theprevious reaction in 3.5 mL of acetonitrile and 0.15 mL of pyridine at0° C. was added 0.50 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 31.2 mg of material which was purified byrecrystallization with ether/hexane to give 24.2 mg (57%) of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-O-acetyl-10-desacetyltaxol.

m.p.148-150.5° C.; [α]²⁵ Na -56.9° (c 0.0024, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11(d, J=7.3 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 7.42(m, 1H,furyl), 6.38(m, 1H, furyl), 6.33(m, 1H, furyl), 6.23(dd, J=8.2, 0.9 Hz,1H, H13), 5.69(d, J=6.9 Hz, 1H, H2), 5.48(dd, J=10.5, 7.3 Hz, 1H, H3'),5.35(d, J=8.7 Hz, H7), 5.33(s, 1H, H10), 5.24(d, J=9.2 Hz, 1H, NH), 4.93(dd, J=9.6, 1.8 Hz, 1H, H5), 4.71(s, 1H, H2'), 4.33(d, J=8.7 Hz, 1H,H20α), 4.21(d, J=8.7 Hz, 1H, H20β), 4.02(d, J=6.9, 1H, H3), 3.98(d,J=1.8 Hz, 1H, 10 OH), 3.29(d, J=5.5 Hz, 1H, 2'OH), 2.53(m, 1H, H6α),2.41(s, 3H, 4Ac), 2.33(m, 2H, H14α), 2.30 (m, 1H, H14β), 1.99 (s, 3H, 7Ac), 1.96 (br s, 3H, Me18), 1.93 (m, 1H, H6β), 1.85 (s, 3H, Me19), 1.62(s, 1H, 1 OH), 1.36 (s, 9H, 3Me t-buthoxy), 1.22 (s, 3H, Me17), 1.10 (s,3H, Me16).

EXAMPLE 52 ##STR75## Preparation of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxyTaxol

To a solution of 7-deshydroxy baccatin (III) (50.0 mg, 0.082 mmol) in1.0 mL of THF at -45° C. was added dropwise 0.09 mL of a 0.98 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(94.2 mg, 0.25 mmol) in 1.0 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 63.8 mg of amixture containing(2'R,3'S)-2'-O-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 63.8 mg (0.067 mmol) of the mixture obtained from theprevious reaction in 5.5 mL of acetonitrile and 0.24 mL of pyridine at0° C. was added 0.8 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 59.2 mg of material which was purified by flashchromatography to give 54.2 mg (96%) of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxytaxol, which was recrystallized from methanol/water.

m.p.148-151° C.; [α]²⁵ Na -50.2° (c 0.0025, CHCl₃). ¹ H NMR (CDCl₃, 300MHz) δ 8.13(d, J=7.1 Hz, 2H, benzoate ortho), 7.60(m, 1H, benzoatepara), 7.49(m, 2H, benzoate meta), 7.27(dd, J=5.1, 1.2 Hz, 1H, thienyl),7.07(d, J=3.3 Hz, 1H, thienyl), 7.01(dd, J=5.1, 3.3 Hz, 1H, thienyl),6.43(s, 1H, H10), 6.23(dd, J=9.0, 0.9 Hz, 1H, H13), 5.68(d, J=7.2 Hz,1H, H2), 5.50(d, J=9.6 Hz, 1H, H3'), 5.32(d, J=7.2 Hz, 1H, NH), 4.93(dd,J=9.0, 2.1 Hz, 1H, H5), 4.64(d, J=3.3 Hz, 1H, H2'), 4.33(d, J=9.0 Hz,1H, H20α), 4.19(d, J=9.0 Hz, 1H, H20β), 3.76(d, J=6.6 Hz, 1H, H3),3.43(m, 1H, 2'OH), 2.38(s, 3H, 4Ac), 2.34(m, 1H, H14α), 2.31(m, 1H,H14β), 2.28(m, 1H, H6α), 2.08(m, 1H, H7α), 1.95(m, 1H, H6β), 1.86(br s,3H, Me18), 1.71(s, 3H, Me19), 1.66(s, 1H, 1 OH), 1.57(m, 1H, H7β),1.30(s, 9H, 3Me t-buthoxy), 1.24(s, 3H, Me16), 1.16(s, 3H, Me17).

EXAMPLE 53 ##STR76## Preparation of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxyTaxol

To a solution of 7-deshydroxy baccatin (III) (40.0 mg, 0.065 mmol) in0.8 mL of THF at -45° C. was added dropwise 0.08 mL of a 0.98 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(71.8 mg, 0.20 mmol) in 1.0 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 56.0 mg of amixture containing(2'R,3'S)-2'-O-triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 56.0 mg (0.060 mmol) of the mixture obtained from theprevious reaction in 4.5 mL of acetonitrile and 0.20 mL of pyridine at0° C. was added 0.66 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 45.7 mg of material which was purified by flashchromatography to give 37.2 mg (75%) of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxytaxol, which was recrystallized from methanol/water.

m.p.143-146° C.; [α]²⁵ Na -56.2° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=7.1 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.48(m, 2H, benzoate meta), 7.41(m, 1H,furyl), 6.42(s, 1H, H10), 6.38(m, 1H, furyl), 6.33(m, 1H, furyl),6.22(dd, J=9.0, 0.9 Hz, 1H, H13), 5.66(d, J=7.2 Hz, 1H, H2), 5.42(d,J=9.6 Hz, 1H, H3'), 5.27(d, J=7.2 Hz, 1H, NH), 4.92(dd, J=9.0, 2.1 Hz,1H, H5), 4.61(d, J=3.3 Hz, 1H, H2'), 4.32(d, J=9.0 Hz, 1H, H20α),4.20(d, J=9.0 Hz, 1H, H20β), 3.77(d, J=6.6 Hz, 1H, H3), 3.41(m, 1H,2'OH), 2.37(s, 3H, 4Ac), 2.32(m, 1H, H14α), 2.29(m, 1H, H14β), 2.22(m,1H, H6α), 2.06(m, 1H, H7α), 1.92(m, 1H, H6β), 1.86(br s, 3H, Me18),1.70(s, 3H, Me19), 1.64(s, 1H, 1 OH), 1.55(m, 1H, H7β), 1.30(s, 9H, 3Met-buthoxy), 1.25(s, 3H, Me16), 1.16(s, 3H, Me17).

EXAMPLE 54 ##STR77## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy Taxol

To a solution of 7-deshydroxy baccatin (III) (40.0 mg, 0.065 mmol) in0.8 mL of THF at -45° C. was added dropwise 0.08 mL of a 0.98 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(phenyl)azetidin-2-one (73.7mg, 0.20 mmol) in 0.8 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 54.6 mg of amixture containing(2'R,3'S)-2'-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxytaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 54.6 mg (0.055 mmol) of the mixture obtained from theprevious reaction in 4.5 mL of acetonitrile and 0.20 mL of pyridine at0° C. was added 0.66 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 47.7 mg of material which was purified by flashchromatography to give 33.9 mg (74%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-7-deshydroxy taxol, which wasrecrystallized from methanol/water.

m.p.149-152° C.; [α]²⁵ Na -51.3° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=7.1 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 7.43-7.29(m, 5H,phenyl), 6.45(s, 1H, H10), 6.25(dd, J=9.3, 0.9 Hz, 1H, H13), 5.66(d,J=7.2 Hz, 1H, H2), 5.38(d, J=9.9 Hz, 1H, H3'), 5.26(d, J=7.5 Hz, 1H,NH), 4.93(dd, J=9.0, 2.1 Hz, 1H, H5), 4.61(br s, 1H, H2'), 4.36(d, J=9.0Hz, 1H, H20α), 4.20(d, J=9.0 Hz, 1H, H20β), 3.76(d, J=6.6 Hz, 1H, H3),3.32(m, 1H, 2'OH), 2.37(s, 3H, 4Ac), 2.34(m, 1H, H14α), 2.32(m, 1H,H14β), 2.28(m, 1H, H6α), 2.05(m, 1H, H7α), 1.94(m, 1H, H6β), 1.84(br s,3H, Me18), 1.73(s, 3H, Me19), 1.65(s, 1H, 1 OH), 1.56(m, 1H,H7β),1.31(s, 9H, 3Me t-buthoxy), 1.23(s, 3H, Me16), 1.15(s, 3H, Me17).

EXAMPLE 55 ##STR78## Preparation of10-deacetyl-9-desoxo-9β-hydroxy-N-debenzoyl-N-(t-butoxycarbonyl) Taxol

To a solution of 7,10-(bis)triethylsilyl-10-deacetyl-9-desoxo-9β-hydroxybaccatin III (95 mg, 0.123 mmol) in 1 mL of THF at -45° C. was addeddropwise 0.250 mL of a 0.98M solution of (TMS)₂ NLi in THF. After 1 h at-45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (137mg, 0.37 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was gradually warmed to 0° C. during 6h before 1 mL of aqueoussolution was added. The mixture was partitioned between saturatedaqueous NaHCO₃ and ethyl acetate. Evaporation of the organic layer gavea residue which was purified by flash chromatography to afford 127 mg of(2'R,3'S)-2',7,10-(tris)triethylsilyl-10-deacetyl-9-desoxo-9β-hydroxy-N-debenzoyl-N-(t-butoxycarbonyl)taxol and 8 mg of the (2'S,3'R) isomer.

To a solution of 90 mg of the major compound obtained from the previousreaction in 1.5 mL of acetonitrile and 2 mL of pyridine at 0° C. wasadded 0.8 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 24 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 71 mg of material which was purified by flashchromatography to give 58 mg (92%) of10-deacetyl-9-desoxo-9β-hydroxy-N-debenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from ethyl acetate/ether/hexane.

m.p. 160-161° C.; [α]²⁵ Na -18.75° (c 0.08, CHCl₃).

¹ H NMR (CD₃ OD, 500 MHz) δ 8.10 (d, J=7.0 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (m, 2H, benzoate, meta), 7.41 (d, J=8.0Hz, 2H, phenyl, ortho), 7.36 (m, 2H, phenyl, meta), 7.28 (m, 1H, phenyl,para),6.18 (m, 1H, H13), 6.18 (d, J=5.5 Hz, 1H, H2β), 5.18 (br s, 1H,H3'), 5.10 (d, J=5.5 Hz, 1H, H10), 4.99 (d, J=8.2 Hz, 1H, H5), 4.91 (d,J=9.3 Hz, 1H, NH), 4.59 (br s, 1H, H2'), 4.51 (d, J=5.5 Hz, 1H, H9),4.22(d, J=8.0 Hz, 1H, H20α), 4.16 (d, J=8.0 Hz, 1H, H20β), 3.86 (dd,J=9.5, 7.5 Hz, 1H, H7), 3.13 (d, J=5.5 Hz, 1H, H3), 2.48 (m, 1H, H6α),2.29 (m, 1H, H14α), 2.28 (s, 3H, 4Ac), 2.19 (m, 1H, H14β), 1.85 (ddd,J=15.1, 9.6, 1.4 Hz, 1H, H6β), 1.79 (s, 3H, Me16), 1.78 (s, 3H, Me18),1.61 (s, 3H, Me19H), 1.42 (s, 9H, t-Bu), 1.29 (s, 3H, Me17).

EXAMPLE 56 ##STR79## Preparation of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9.beta.-hydroxy-10-desacetylTaxol

To a solution of7,10-(bis)-O-triethylsilyl-9-desoxo-9β-hydroxy-10-deacetyl baccatin(III) (70.0 mg, 0.09 mmol) in 1.0 mL of THF at -45° C. was addeddropwise 0.10 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-thienyl)azetidin-2-one(103.8 mg, 0.27 mmol) in 1.0 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 97.4 mg of amixture containing(2'R,3'S)-2',7,10-(tris)-O-triethylsilyl-3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9β-hydroxy-10-desacetyl taxol and a small amount of the(2'S,3'R) isomer.

To a solution of 97.4 mg (0.084 mmol) of the mixture obtained from theprevious reaction in 13.5 mL of acetonitrile and 0.57 mL of pyridine at0° C. was added 1.92 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 69.4 mg of material which was purified by flashchromatography to give 63.1 mg (89%) of3'-desphenyl-3'-(2-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9.beta.-hydroxy-10-desacetyltaxol, which was recrystallized from methanol/water.

m.p.146-148° C.; [α]²⁵ Na -54.2° (c 0.0026, CHCl₃).

¹ H NMR (MeOH, 300 MHz) δ 8.11(d, J=7.1 Hz, 2H, benzoate ortho), 7.61(m,1H, benzoate para), 7.48(m, 2H, benzoate meta), 7.25(dd, J=5.4, 1.2 Hz,1H, thienyl), 7.14(d, J=3.3 Hz, 1H, thienyl), 7.03(dd, J=5.4, 3.9 Hz,1H, thienyl), 6.18(m, 1H, H13), 6.18(d, J=5.5 Hz, 1H, H2), 5.23(br s,1H, H3'), 5.07(d, J=5.5 Hz, 1H, H10), 4.97(d, J=8.1 Hz, 1H, H5), 4.84(d,J=9.3 hz, 1H, NH), 4.52(br s, 1H, H2'), 4.50(d, J=5.5 Hz, 1H, H9),4.23(d, J=8.1, 1H, H20α), 4.16(d, J=8.1 Hz, 1H, H20β), 3.92(dd, J=9.4,7.5 Hz, 1H, H7), 3.13(d, J=5.5 Hz, H3), 2.47(m, 1H, H6α), 2.26(m, 1H,H14α), 2.27(s, 3H, 4Ac), 2.16(m, 1H, H14β), 1.84(ddd, J=15.1, 9.4, 1.2Hz, H6β), 1.79(s, 3H, Me16), 1.76(s, 3H, Me18), 1.62(s, 3H, Me19)1.39(s, 9H, 3Me t-butoxy), 1.27(s, 3H, Me17).

EXAMPLE 57 ##STR80## Preparation of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9.beta.-hydroxy-10-desacetylTaxol

To a solution of7,10-(bis)-O-triethylsilyl-9-desoxo-9β-hydroxy-10-deacetyl baccatin(III) (70.0 mg, 0.09 mmol) in 1.0 mL of THF at -45° C. was addeddropwise 0.10 mL of a 0.98 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-(2-furyl)azetidin-2-one(99.5 mg, 0.27 mmol) in 1.0 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 94.3 mg of amixture containing(2'R,3'S)-2',7,10-(tris)-O-triethylsilyl-3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9β-hydroxy-10-desacetyl taxol and a small amount of the(2'S,3'R) isomer.

To a solution of 94.3 mg (0.082 mmol) of the mixture obtained from theprevious reaction in 13.5 mL of acetonitrile and 0.57 mL of pyridine at0° C. was added 1.92 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 72.3 mg of material which was purified by flashchromatography to give 59.1 mg (89%) of3'-desphenyl-3'-(2-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)-9-desoxo-9.beta.-hydroxy-10-desacetyltaxol, which was recrystallized from methanol/water.

m.p.144-146° C.; [α]²⁵ Na -54.0° (c 0.0028, CHCl₃).

¹ H NMR (MeOH, 300 MHz) δ 8.10(d, J=7.1 Hz, 2H, benzoate ortho), 7.60(m,1H, benzoate para), 7.51(m, 2H, benzoate meta), 7.40(m, 1H, furyl),6.37(m, 1H, furyl), 6.34(m, 1H, furyl), 6.17(m, 1H, H13), 6.16(d, J=5.4Hz, 1H, H2), 5.24(br s., 1H, H3'), 5.11(d, J=5.5 Hz, 1H, H10), 4.86(d,J=8.1 Hz, 1H, H5), 4.83(d, J=9.3 hz, 1H, NH), 4.50(d, J=5.5 Hz, 1H, H9),4.45(br s, 1H, H2'), 4.21(d, J=8.1, 1H, H20α), 4.13(d, J=8.1 Hz, 1H,H20β), 3.92(dd, J=9.4, 7.5 Hz, 1H, H7), 3.11(d, J=5.5 Hz, H3), 2.46(m,1H, H6α), 2.24(m, 1H, H14α), 2.21(s, 3H, 4Ac), 2.15(m, 1H, H14β),1.79(ddd, J=15.1, 9.4, 1.2 Hz, H6β), 1.77(s, 3H, Me16), 1.73(s, 3H,Me18), 1.61(s, 3H, Me19), 1.37(s, 9H, 3Me t-buthoxy), 1.26(s, 3H, Me17).

EXAMPLE 58 ##STR81## Preparation of2-desbenzoyl-2-(3-methoxybenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)Taxol

To a solution of2-desbenzoyl-2-(3-methoxybenzoyl)-10-deacetyl-7,10-bis(triethylsilyl)baccatin III (48.2 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 70.8 mg of amixture containing(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(3-methoxybenzoyl)-10-deacetyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 70.8 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 50.3 mg of material which was purified byrecrystallization to give 43.1 mg (86%) of2-desbenzoyl-2-(3-methoxybenzoyl)-10-deacetyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol.

m.p.162-164° C.; [α]²⁵ Na -61.6° (c 0.790, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 7.67 (m, 2H, methoxybenzoate, ortho), 7.36(m, 6H, aromatic), 7.15 (m, 1H, methoxybenzoate), 6.19 (m, 1H, H13),5.65 (d, J=6.9 Hz, 1H, H2β), 5.50 (m, 1H, NH), 5.21 (m, 2H, H3', H10),4.95 (dd, J=7.8, 1.8 Hz, 1H, H5), 4.60 (m, 1H, H2'), 4.33 (d, J=8.7 Hz,1H, H20α), 4.23 (m, 1H, H7), 4.17 (d, J=8.7 Hz, 1H, H20β), 3.89 (d,J=6.9 Hz, 1H, H3), 3.86 (s, 3H, methoxy), 3.56 (m, 1H, 2'OH), 2.55 (m,1H, H6α), 2.34 (s, 3H, 4Ac), 2.23 (m, 2H, H14), 1.83 (s, 3H, Me18), 1.79(m, 1H, H6β), 1.73 (s, 3H, Me19), 1.32 (s, 9H, t-butyl), 1.22 (s, 3H,Me17), 1.11 (s, 3H, Me16).

EXAMPLE 59 ##STR82## Preparation of2-desbenzoyl-2-(3-methylbenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)Taxol

To a solution of2-desbenzoyl-2-(3-methylbenzoyl)-10-deacetyl-7,10-bis(triethylsilyl)baccatin III (47.2 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 70.0 mg of amixture containing(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(3-methyl-benzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 70.0 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 49.3 mg of material which was purified byrecrystallization to give 41.9 mg (85%) of2-desbenzoyl-2-(3-methylbenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol.

m.p.169-171° C.; [α]²⁵ Na -60.4° (c 0.510, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 7.91 (m, 2H, benzoate), 7.38 (m, 7H,aromatic), 6.21 (m, 1H, H13), 5.65 (d, J=7.2 Hz, 1H, H2β), 5.42 (m, 1H,NH), 5.26 (m, 1H, H3'), 5.20 (d, J=1.2 Hz, 1H, H10), 4.94 (m, 1H, H5),4.61 (m, 1H, H2'), 4.31 (d, J=8.7 Hz, 1H, H20α), 4.24 (m, 1H, H7), 4.17(d, J=8.7 Hz, 1H, H20β), 3.91 (d, J=7.2 Hz, 1H, H3), 3.37 (m, 1H, 2'OH),2.57 (m, 1H, H6α), 2.43 (s, 3H, 4Ac), 2.26 (m, 2H, H14), 2.17 (s, 3H,methylbenzoate), 1.84 (s, 3H, Me18), 1.79 (m, 1H, H6β), 1.74 (s, 3H,Me19), 1.33 (s, 9H, t-butyl), 1.22 (s, 3H, Me17), 1.12 (s, 3H, Me16).

EXAMPLE 60 ##STR83## Preparation of2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)Taxol

To a solution of2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-7,10-bis(triethylsilyl)baccatin III (48.4 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 71 mg of a mixturecontaining(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(3-chloro-benzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 71 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 50.5 mg of material which was purified byrecrystallization to give 40.4 mg (80%) of2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol.

m.p.149-150° C.; [α]²⁵ Na -53.3° (c 0.510, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (br s, 1H, chlorobenzoate ortho), 7.98(d, J=7.5 Hz, 1H, chlorobenzoate ortho), 7.59 (m, 1H, chlorobenzoate),7.45 (t, J=7.5 Hz, 1H, chlorobenzoate), 7.38 (m, 5H, aromatic), 6.18 (m,1H, H13), 5.62 (d, J=7.2 Hz, 1H, H2β), 5.41 (m, 1H, H3'), 5.24 (m, 1H,NH), 5.20 (d, J=1.0 Hz, 1H, H10), 4.95 (dd, J=9.3, 1.2 Hz, 1H, H5), 4.59(m, 1H, H2'), 4.30 (d, J=8.4 Hz, 1H, H20α), 4.23 (m, 1H, H7), 4.15 (d,J=8.4 Hz, 1H, H20β), 3.91 (d, J=7.2 Hz, 1H, H3), 3.35 (m, 1H, 2'OH),2.58 (m, 1H, H6α), 2.36 (s, 3H, 4Ac), 2.24 (m, 2H, H14), 1.84 (s, 3H,Me18), 1.79 (m, 1H, H6β), 1.75 (s, 3H, Me19), 1.34 (s, 9H, t-butyl),1.23 (s, 3H, Me17), 1.12 (s, 3H, Me16).

EXAMPLE 61 ##STR84## Preparation of2-desbenzoyl-2-(3-trifluoromethylbenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)Taxol

To a solution of2-desbenzoyl-2-(3-trifluoromethylbenzoyl)-10-deacetyl-7,10-bis(triethylsilyl)baccatin III (50.4 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 73.0 mg of amixture containing(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(3-trifluoromethylbenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 73.0 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 52.6 mg of material which was purified byrecrystallization to give 41.0 mg (78%) of2-desbenzoyl-2-(3-trifluoromethylbenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol.

m.p.140-142° C.; [α]²⁵ Na -50.4° (c 1.055, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.43 (s, 1H, benzoate, ortho), 8.29 (d, J=7.8Hz, 1H, benzoate ortho), 7.88 (d, J=7.8 Hz, 1H, benzoate), 7.66 (t,J=7.8 Hz, 1H, benzoate), 7.38 (m, 5H, aromatic), 6.17 (m, 1H, H13), 5.65(d, J=7.2 Hz, 1H, H2β), 5.38 (m, 1H, NH), 5.23 (m, 1H, H3'), 5.21 (d,J=1.8 Hz, 1H, H10), 4.95 (m, 1H, H5), 4.58 (m, 1H, H2'), 4.27 (d, J=8.7Hz, 1H, H20α), 4.21 (m, 1H, H7), 4.15 (d, J=8.7 Hz, 1H, H20β), 3.93 (d,J=7.2 Hz, 1H, H3), 3.35 (m, 1H, 2'OH), 2.59 (m, 1H, H6α), 2.33 (s, 3H,4Ac), 2.23 (m, 2H, H14), 1.85 (s, 3H, Me18), 1.79 (m, 1H, H6β), 1.76 (s,3H, Me19), 1.32 (s, 9H, t-butyl), 1.22 (s, 3H, Me17), 1.11 (s, 3H,Me16).

EXAMPLE 62 ##STR85## Preparation of2-desbenzoyl-2-(4-methoxybenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)Taxol

To a solution of2-desbenzoyl-2-(4-methoxybenzoyl)-10-deacetyl-7,10-bis(triethylsilyl)baccatin III (48.2 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 71 mg of a mixturecontaining(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(4-methoxybenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 71 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 50.3 mg of material which was purified byrecrystallization to give 45.2 mg (90%) of2-desbenzoyl-2-(4-methoxybenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol.

m.p.160-162° C.; [α]²⁵ Na -47.6° (c 0.290, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.05 (dd, J=9.0, 2H, methoxybenzoate, ortho),7.38 (m, 5H, aromatic), 6.96 (dd, J=9.0, 2H, methoxybenzoate, meta),6.23 (m, 1H, H13), 5.64 (d, J=7.2 Hz, 1H, H2β), 5.42 (m, 1H, H3'), 5.27(m, 1H, NH), 5.19 (d, J=1.2 Hz, 1H, H10), 4.93 (dd, J=7.8, 1.8 Hz, 1H,H5), 4.62 (m, 1H, H2'), 4.31 (d, J=9.0 Hz, 1H, H20α), 4.24 (m, 1H, H7),4.19 (d, J=9.0 Hz, 1H, H20β), 3.89 (d, J=7.2 Hz, 1H, H3), 3.65 (s, 3H,methoxy), 3.32 (m, 1H, 2'OH), 2.58 (m, 1H, H6α), 2.37 (s, 3H, 4Ac), 2.26(m, 2H, H14), 1.85 (s, 3H, Me18), 1.78 (m, 1H, H6β), 1.75 (s, 3H, Me19),1.34 (s, 9H, t-butyl), 1.23 (s, 3H, Me17), 1.12 (s, 3H, Me16).

EXAMPLE 63 ##STR86## Preparation of2-desbenzoyl-2-(4-chlorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)Taxol

To a solution of2-desbenzoyl-2-(4-chlorobenzoyl)-10-deacetyl-7,10-bis(triethylsilyl)baccatin III (48.4 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 71 mg of a mixturecontaining(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(4-chlorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 71 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 51 mg of material which was purified by recrystallizationto give 37.9 mg (75%) of2-desbenzoyl-2-(4-chlorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol.

m.p.160-161° C.; [α]²⁵ Na -46.0° (c 0.104, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.03 (d, J=8.7 Hz, 2H, chlorobenzoate ortho),7.48 (d, J=8.7 Hz, 2H, chlorobenzoate meta), 7.38 (m, 5H, aromatic),6.23 (m, 1H, H13), 5.64 (d, J=7.2 Hz, 1H, H2β), 5.45 (m, 1H, H3'), 5.26(m, 1H, NH), 5.20 (d, J=1.2 Hz, 1H, H10), 4.93 (d, J=7.8 Hz, 1H, H5),4.63 (m, 1H, H2'), 4.28 (d, J=8.2 Hz, 1H, H20α), 4.22 (m, 1H, H7), 4.15(d, J=8.2 Hz, 1H, H20β), 3.90 (d, J=7.2 Hz, 1H, H3), 3.36 (m, 1H, 2'OH),2.58 (m, 1H, H6α), 2.37 (s, 3H, 4Ac), 2.25 (m, 2H, H14), 1.85 (s, 3H,Me18), 1.80 (m, 1H, H6β), 1.75 (s, 3H, Me19), 1.32 (s, 9H, t-butyl),1.23 (s, 3H, Me17), 1.11 (s, 3H, Me16).

EXAMPLE 64 ##STR87## Preparation of2-desbenzoyl-2-(4-fluorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)Taxol

To a solution of2-desbenzoyl-2-(4-fluorobenzoyl)-10-deacetyl-7,10-bis(triethylsilyl)baccatin III (47.5 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 70 mg of a mixturecontaining(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(4-fluorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 70 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 49.5 mg of material which was purified byrecrystallization to give 42.0 mg (85%) of2-desbenzoyl-2-(4-fluorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol.

m.p. 158-160° C.; [α]²⁵ Na -47.6° (c 0.290, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13 (m, 2H, fluorobenzoate ortho), 7.38 (m,5H, aromatic), 7.17 (m, 2H, fluorobenzoate), 6.23 10 (m, 1H, H13), 5.64(d, J=7.2 Hz, 1H, H2β), 5.41 (d, J=9.9 Hz, 1H, H3'), 5.26 (m, 1H, NH),5.20 (d, J=1.2 Hz, 1H, H10), 4.93 (dd, J=9.9, 2.1 Hz, 1H, H5), 4.63 (m,1H, H2'), 4.28 (d, J=8.2 Hz, 1H, H20α), 4.24 (m, 1H, H7), 4.17 (d, J=8.2Hz, 1H, H20β), 3.91 (d, J=7.2 Hz, 1H, H3), 3.32 (m, 1H, 2'OH), 2.58 (m,1H, H6α), 2.37 (s, 3H, 4Ac), 2.25 (m, 2H, H14), 1.85 (s, 3H, Me18), 1.80(m, 1H, H6β), 1.75 (s, 3H, Me19), 1.33 (s, 9H, t-butyl), 1.25 (s, 3H,Me17), 1.12 (s, 3H, Me16).

EXAMPLE 65 ##STR88## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(2-trifluoromethylbenzoyl)-10-desacetylTaxol

To a solution of2-desbenzoyl-2-(2-trifluoromethylbenzoyl)-10-deacetyl-7,10-(bis)-O-triethylsilylbaccatin III (50.4 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in 10 hexane.After 0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 73.0 mg of amixture containing(2'R,3'S)-2',7,10-(tris)-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(2-trifluoromethylbenzoyl)-10-desacetyltaxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 73.0 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 52.6 mg of material which was purified byrecrystallization to give 39.4 mg (75%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(2-trifluoromethylbenzoyl)-10-desacetyltaxol.

m.p.121-123° C.; [α]²⁵ Na -34.2° (c 0.760, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.10 (m, 1H, benzoate, ortho), 7.82 (d, J=7.5Hz, 1H, benzoate), 7.70 (m, 2H, benzoate), 7.35 (m, 5H, aromatic), 6.24(m, 1H, H13), 5.64 (d, J=7.2 Hz, 1H, H2β), 5.46 (m, 1H, NH), 5.28 (m,1H, H3'), 5.19 (d, J=1.8 Hz, 1H, H10), 4.89 (dd, J=8.7, 1.2 Hz, 1H, H5),4.63 (m, 1H, H2'), 4.26 (d, J=8.1 Hz, 1H, H20α), 4.17 (m, 2H, H7, H20β),3.90 (d, J=7.2 Hz, 1H, H3), 3.35 (m, 1H, 2'OH), 2.56 (m, 1H, H6α), 2.39(m, 2H, H14), 2.24 (s, 3H, 4Ac), 1.87 (s, 3H, Me18), 1.84 (m, 1H, H6β),1.76 (s, 3H, Me19), 1.38 (s, 9H, t-butyl), 1.24 (s, 3H, Me17), 1.11 (s,3H, Me16).

EXAMPLE 66 ##STR89## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(2-methylbenzoyl)-10-desacetylTaxol

To a solution of2-desbenzoyl-2-(2-methylbenzoyl)-10-desacetyl-7,10-(bis)-O-triethylsilylbaccatin III (47.2 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 70.0 mg of amixture containing(2'R,3'S)-2',7,10-(tris)-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(2-methylbenzoyl)-10-desacetyltaxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 70.0 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 49.3 mg of material which was purified byrecrystallization to give 44.4 mg (90%) of2-desbenzoyl-2-(2-methylbenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl)taxol.

m.p.129-131° C.; [α]²⁵ Na -50.8° (C 0.750, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.05 (m, 1H, benzoate), 7.38 (m, 8H,aromatic), 6.21 (m, 1H, H13), 5.65 (d, J=6.6 Hz, 1H, H2β), 5.46 (m, 1H,NH), 5.24 (m, 1H, H3'), 5.20 (d, J=0.9 Hz, 1H, H10), 4.91 (dd, J=9.3,1.5 Hz, 1H, H5), 4.60 (br s, 1H, H2'), 4.25 (d, J=8.1 Hz, 1H, H20α),4.24 (m, 1H, H7), 4.17 (d, J=8.1 Hz, 1H, H20β), 3.88 (d, J=6.6 Hz, 1H,H3), 3.37 (m, 1H, 2'OH), 2.63 (s, 3H, methylbenzoate), 2.57 (m, 1H,H6α), 2.30 (s, 3H, 4Ac), 2.58 (m, 2H, H14), 1.83 (s, 3H, Me18), 1.79 (m,1H, H6β), 1.75 (s, 3H, Me19), 1.37 (s, 9H, t-butyl), 1.24 (s, 3H, Me17),1.13 (s, 3H, Me16).

EXAMPLE 67 ##STR90## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3,5-bis(trifluoromethyl)benzoyl)-10-desacetylTaxol

To a solution of2-desbenzoyl-2-(3,5-bis(trifluoromethyl)benzoyl)-7,10-(bis)-O-triethylsilyl-10-desacetylbaccatin III (51.3 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 73.9 mg of amixture containing(2'R,3'S)-2',7,10-(tris)-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3,5-bis(trifluoromethyl)benzoyl)-10-desacetyltaxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 73.9 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 53.4 mg of material which was purified byrecrystallization to give 49.1 mg (92%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3,5-bis(trifluoromethyl)-benzoyl)-10-desacetyltaxol.

m.p.141-143° C.; [α]²⁵ Na -43.6° (c 0.730, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.59 (s, 2H, benzoate, ortho), 8.12 (s, 1H,benzoate para), 7.37 (m, 5H, aromatic), 6.14 (m, 1H, H13), 5.64 (d,J=7.2 Hz, 1H, H2β), 5.36 (m, 1H, NH), 5.21 (d, J=1.2 Hz, 1H, H10), 5.18(m, 1H, H3'), 4.97 (dd, J=9.6, 2.1 Hz, 1H, H5), 4.58 (m, 1H, H2'), 4.19(m, 3H, H20, H7), 3.95 (d, J=7.2 Hz, 1H, H3), 3.39 (m, 1H, 2'OH), 2.59(m, 1H, H6α), 2.30 (s, 3H, 4Ac), 2.25 (m, 2H, H14), 1.85 (s, 3H, Me18),1.79 (m, 1H, H6β), 1.75 (s, 3H, Me19), 1.32 (s, 9H, t-butyl), 1.22 (s,3H, Me17), 1.13 (s, 3H, Me16).

EXAMPLE 68 ##STR91## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3,5-dimethylbenzoyl)-10-desacetoxyTaxol

To a solution of2-desbenzoyl-2-(3,5-dimethylbenzoyl)-7,10-(bis)-O-triethylsilyl-10-desacetylbaccatin III (48.1 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 70.1 mg of amixture containing(2'R,3'S)-2',7,10-(tris)-O-triethylsilyl-N-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3,5-dimethylbenzoyl)-10-desacetoxytaxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 70.1 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 50.2 mg of material which was purified byrecrystallization to give 45.1 mg (90%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3,5-dimethylbenzoyl)-10-desacetoxytaxol.

m.p.198-200° C.; [α]²⁵ Na -49.0° (c 0.965, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 7.72 (s, 2H, benzoate, ortho), 7.37 (m, 5H,aromatic), 7.23 (s, 1H, benzoate, para), 6.21 (m, 1H, H13), 5.64 (d,J=7.2 Hz, 1H, H2β), 5.45 (m, 1H, NH), 5.25 (m, 1H, H3'), 5.20 (d, J=1.8Hz, 1H, H10), 4.94 (dd, J=9.3, 1.2 Hz, 1H, H5), 4.61 (m, 1H, H2'), 4.32(d, J=8.1 Hz, 1H, H20α), 4.21 (m, 1H, H7), 4.16 (d, J=8.7 Hz, 1H, H20β),3.89 (d, J=7.2 Hz, 1H, H3), 3.39 (m, 1H, 2'OH), 2.58 (m, 1H, H6α), 2.38(s, 6H, dimethylbenzoate), 2.36 (s, 3H, 4Ac), 2.27 (m, 2H, H14), 1.88(m, 1H, H6β), 1.83 (s, 3H, Me18), 1.74 (s, 3H, Me19), 1.33 (s, 9H,t-butyl), 1.22 (s, 3H, Me17), 1.12 (s, 3H, Me16).

EXAMPLE 69 ##STR92## Preparation ofN-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-isopropyl Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.072 mmol) in0.5 mL of THF at -45° C. was added dropwise 0.05 mL of a 1.64 M solutionof n-BuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-ethoxycarbonyl-3-triethylsilyloxy-4-isopropyl azetidin-2-one (31.8mg, 0.100 mmol) in 0.3 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 54.2 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-isopropyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 54.2 mg (0.053 mmol) of the mixture obtained from theprevious reaction in 3 mL of acetonitrile and 0.14 mL of pyridine at 0°C. was added 0.42 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 53.8 mg of material which was purified by flashchromatography to give 33.9 mg (78%) ofN-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-isopropyl taxol, whichwas recrystallized from methanol/water.

m.p.147-148° C.; [α]²⁵ Na -55.0° (c 0.002.2, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.1 Hz, 2H, benzoate ortho),7.62(m, 1H, benzoate para), 7.53(m, 2H, benzoate meta), 6.30(s, 1H,H10), 6.25 (dd, J=7.7, 7.7 Hz, 1H, H13), 5.69(d, J=7.1 Hz, 1H, H2β),4.97(d, J=7.7, 1H, H5), 4.86(d, J=8.2 Hz, 1H, NH), 4.52(m, 1H, H2'),4.41(m, 1H, H7), 4.32(d, J=7.8 Hz, 1H, H20α), 4.20(d, J=7.8 Hz, 1H,H20β), 3.95(q, J=6.6 Hz, 2H, --CH₂ CH₃ ethoxy), 3.81 (d, J=7.1 Hz, 1H,H3), 3.75(ddd, J=8.8, 8.8, 3.3 Hz, 1H, H3'), 3.19 (d, J=6.6 Hz, 1H,2'OH), 2.54(m, 1H, H6α), 2.47(d, J=3.9 Hz, 1H, 7OH), 2.42(s, 3H, 4Ac),2.38(m, 2H, H14), 2.24(s, 3H, 10Ac), 2.22(br s, 3H, Me18), 1.98 (m, 1H,CH3CHCH3 isopropyl) 1.89 (m, 1H, H6β), 1.87(s, 3H, Me19), 1.26(s, 3H,Me17), 1.18(s, 3H, Me16), 1.09(t, J=6.6 Hz, 3H, Me ethoxy), 1.08(d,J=6.6 Hz, 3H, Me isopropyl), 1.03(d, J=6.6 Hz, 3H, Me isopropyl).

EXAMPLE 70 ##STR93## Preparation ofN-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-(isopropyl) Taxol

To a solution of 7-triethylsilyl baccatin III (25.0 mg, 0.036 mmol) in0.4 mL of THF at -45° C. was added dropwise 0.04 mL of a 1.00 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-t-butoxycarbonyl-3-triethylsilyloxy-4-isopropyl azetidin-2-one(31.8 mg, 0.100 mmol) in 0.3 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 35.3 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-isopropyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 35.3 mg (0.035 mmol) of the mixture obtained from theprevious reaction in 2 mL of acetonitrile and 0.1 mL of pyridine at 0°C. was added 0.3 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 30.8 mg of material which was purified by flashchromatography to give 20.3 mg (71%) ofN-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-isopropyl taxol, whichwas recrystallized from methanol/water.

m.p.162-163° C.; [α]²⁵ Na -53.0° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.1 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.28(s, 1H,H10), 6.22 (dd, J=7.7, 7.7 Hz, 1H, H13), 5.63(d, J=7.1 Hz, 1H, H2β),4.97(d, J=7.7, 1H, H5), 4.73(d, J=8.2 Hz, 1H, NH), 4.53(m, 1H, H2'),4.41(m, 1H, H7), 4.31(d, J=7.8 Hz, 1H, H20α), 4.19(d, J=7.8 Hz, 1H,H20β), 3.80(d, J=7.1 Hz, 1H, H3), 3.68(ddd, J=8.8, 8.8, 3.3 Hz, 1H,H3'), 3.22 (d, J=6.6 Hz, 1H, 2'OH), 2.54(m, 1H, H6α), 2.48(d, J=3.9 Hz,1H, 7OH), 2.40(s, 3H, 4Ac), 2.38(m, 2H, H14), 2.23(s, 3H, 10Ac), 2.16(brs, 3H, Me18), 1.96(m, 1H, CH₃ CHCH₃ isopropyl) 1.89(m, 1H, H6β), 1.88(s,3H, Me19), 1.33(s, 9H, Me t-Buotoxy), 1.25(s, 3H, Me17), 1.16(s, 3H,Me16), 1.08(d, J=6.6 Hz, 3H, Me isopropyl), 1.03(d, J=6.6 Hz, 3H, Meisopropyl).

EXAMPLE 71 ##STR94## Preparation ofN-debenzoyl-N-(n-butoxycarbonyl)-3'-desphenyl-3'-isopropyl Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.072 mmol) in1.0 mL of THF at -45° C. was added dropwise 0.05 mL of a 1.64 M solutionof n-BuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(n-butoxycarbonyl)-3-triethylsilyloxy-4-isopropyl azetidin-2-one(67.1 mg, 0.215 mmol) in 0.5 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 73.3 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(n-butoxycarbonyl)-3'-desphenyl-3'-isopropyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 73.3 mg (0.07 mmol) of the mixture obtained from theprevious reaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0°C. was added 0.57 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 59.6 mg of material which was purified by flashchromatography to give 44.2 mg (77%) ofN-debenzoyl-N-(n-butoxycarbonyl)-3'-desphenyl-3'-isopropyl taxol, whichwas recrystallized from methanol/water.

m.p.139-141° C.; [α]²⁵ Na -57.5° (c 0.002, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.1 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.30(s, 1H, C10)6.29(d,d, J=7.7, 7.7 Hz, 1H, H13), 5.68 (d, J=7.1 Hz, 1H, H2β), 4.96(d,J=7.7 Hz, 1H, H5), 4.87(d, J=8.2 Hz, 1H, NH), 4.50(m, 1H, H2') 4.42(m,1H, H7), 4.30(d, J=7.8 Hz, H20α), 4.18(d, J=7.8 Hz, 1H, H20β), 3.82(d,J=7.1 Hz, 1H, H3), 3.79(m, 1H, H3') 3.75(t, 2H, J=6.6 Hz, 2H, n-butyl),3.37(d, J=6.6 Hz, 1H, 2'OH), 2.54(m, 1H, H6α), 2.45(d, J=3.9 Hz, 1H,7OH), 2.42(m, 2H, H14), 2.27(s, 3H, 4Ac),, 2.24 (s, 3H, 10Ac), 2.09(brs, 3H, Me18), 1.84 (m, 1H, H6β), 1.68 (s, 3H, Me19), 1.43(brs, 5H,n-butyl and isopropyl), 1.24(s, 3H, Me17), 1.15 (s, 3H, Me16),1.06 (d,J=6.6, Me isopropyl), 1.02(d, J=6.6, Me isopropyl), 0.81(t. J=7.5, Men-butyl).

EXAMPLE 72 ##STR95## Preparation ofN-debenzoyl-N-(2-methylpropanoxycarbonyl)-3'-desphenyl-3'-isopropylTaxol

To a solution of 7-triethylsilyl baccatin III (30.0 mg, 0.043 mmol) in0.5 mL of THF at -45° C. was added dropwise 0.03 mL of a 1.64 M solutionof n-BuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(2-methylpropanoxycarbonyl)-3-triethylsilyloxy-4-isopropylazetidin-2-one(44.2 mg, 0.13 mmol) in 0.5 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 0.2 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 41.6 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-N-debenzoyl-N-(2-methylpropanoxycarbonyl)-3'-desphenyl-3'-isopropyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 41.2 mg (0.039 mmol) of the mixture obtained from theprevious reaction in 2 mL of acetonitrile and 0.1 mL of pyridine at 0°C. was added 0.3 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 33.1 mg of material which was purified by flashchromatography to give 22.6 mg (71%) ofN-debenzoyl-N-(2-methylpropanoxycarbonyl)-3'-desphenyl-3'-isopropyltaxol, which was recrystallized from methanol/water.

m.p.143-145° C.; [α]²⁵ Na -57.9° (c 0.0024, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.1 Hz, 2H, benzoate ortho),7.62(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 6.28(s, 1H,H10), 6.22(dd, J=7.7, 7.7 Hz, 1H, H13), 5.64(d, J=7.1 Hz, 1H, H2β),4.97(d, J=7.7, 1H, H5), 4.83(d, J=8.2 Hz, 1H, NH), 4.51(m, 1H, H2'),4.40(m, 1H, H7), 4.31(d, J=7.8 Hz, 1H, H20α), 4.18(d, J=7.8 Hz, 1H,H20β), 3.80(d, J=7.1 Hz, 1H, H3), 3.76(q, J=6.6 Hz, 2H, --CH₂ CH(CH₃)₂isobutoxy), 3.67 (ddd, J=8.8, 8.8, 3.3 Hz, 1H, H3'), 3.32 (d, J=6.6 Hz,1H, 2'OH), 2.55(m, 1H, H6α), 2.48(d, J=3.9 Hz, 1H, 7OH), 2.42 (s, 3H,4Ac), 2.37(m, 2H, H14), 2.23(s, 3H, 10Ac), 2.18(br s, 3H, Me18), 1.95(m,1H, CH3CHCH3 isopropyl) 1.88(m, 1H, H6β), 1.86 (s, 3H, Me19), 1.62(m,1H, --CH₂ --CH--(CH₃)₂ isopropyl), 1.24(s, 3H, Me17), 1.16(s, 3H, Me16),1.08(d, J=6.6 Hz, 3H, Me isopropyl), 1.03 (d, J=6.6 Hz, 3H, Meisopropyl). 0.88(d, J=6.6 Hz, Me isobutoxy), 0.83(d, J=6.6 Hz, Meisobutoxy).

EXAMPLE 73 ##STR96## Preparation ofN-debenzoyl-N-(isopropoxycarbonyl)-3'-desphenyl-3'-isopropyl Taxol

To a solution of 7-triethylsilyl baccatin III (75.0 mg, 0.092 mmol) in0.8 mL of THF at -45° C. was added dropwise 0.10 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-isopropoxycarbonyl-3-triethylsilyloxy-4-isopropylazetidin-2-one(106.2 mg, 0.32 mmol) in 0.8 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1.0 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 98.3 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(isopropoxycarbonyl)-3'-desphenyl-3'-isopropyltaxol and a small amount of the (2'S'3'R) isomer.

To a solution of 98.3 mg (0.09 mmol) of the mixture obtained from theprevious reaction in 5.0 mL of acetonitrile and 0.23 mL of pyridine at0° C. was added 0.70 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 70.8 mg of material which was purified by flashchromatography to give 58.5 mg (82%) ofN-debenzoyl-N-(isopropoxycarbonyl)-3'-desphenyl-3'-isopropyl taxol,which was recrystallized from methanol/water.

m.p.144-148.5° C.; [α]²⁵ Na -61.0° (c 0.0024, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=6.9 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 6.29(s, 1H,H10), 6.24(dd, J=6.6, 6.6 Hz, 1H, H13), 5.68(d, J=7.2 Hz, 1H, H2β),4.96(d, J=8.4, 1H, H5), 4.81(d, J=6.6 Hz, 1H, NH), 4.70(m, 1H,isopropyloxy), 4.48(m, 1H, H2'), 4.41(m, 1H, H7), 4.31(d, J=8.1 Hz, 1H,H20α), 4.19(d, J=8.1 Hz, 1H, H20β), 3.80(d, J=7.2 Hz, 1H, H3), 3.68(ddd,J=8.8, 8.8, 1.8 Hz, 1H, H3'), 3.33(d, J=5.7 Hz, 1H, 2'OH), 2.53(m, 1H,H6α), 2.46(d, J=3.9 Hz, 1H, 7OH), 2.42(s, 3H, 4Ac), 2.38(m, 2H, H14),2.26(s, 3H, 10Ac), 2.13(br s, 3H, Me18), 1.96(m, 1H, CH3CHCH3isopropyl), 1.90(m, 1H, H6β), 1.88(s, 3H, Me19), 1.75(s, 1H, 10OH),1.25(s, 3H, Me17), 1.16(s, 3H, Me16), 1.14(d, J=6.6 Hz, 3H, Meisopropyloxy), 1.12(d, J=6.6 Hz, 3H, Me isopropyloxy), 1.08(d, J=6.6 Hz,3H, Me isopropyl), 1.03(d, J=6.6 Hz, 3H, Me isopropyl).

EXAMPLE 74 ##STR97## Preparation of3'-desphenyl-3'-isopropyl-N-desbenzoyl-N-(allyloxycarbonyl) Taxol

To a solution of 7-O-triethylsilyl baccatin III (50.0 mg, 0.072 mmol) in0.5 mL of THF at -45° C. was added dropwise 0.05 mL of a 1.64 M solutionof n-BuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-allyloxycarbonyl-3-triethylsilyloxy-4-(isopropyl) azetidin-2-one(70.1 mg, 0.214 mmol) in 0.5 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 0.3 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 61.2 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-isopropyl-N-desbenzoyl-N-(allyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 61.2 mg (0.06 mmol) of the mixture obtained from theprevious reaction in 3.5 mL of acetonitrile and 0.16 mL of pyridine at0° C. was added 0.48 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 57.8 mg of material which was purified by flashchromatography to give 40.3 mg (82%) of3'-desphenyl-3'-isopropyl-N-desbenzoyl-N-(allyloxycarbonyl) taxol, whichwas recrystallized from methanol/water.

m.p.135-136° C.; [α]²⁵ Na -51.1.0° (c 0.0023, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.1 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 6.30(s, 1H,H10), 6.24(dd, J=7.7, 7.7 Hz, 1H, H13), 5.78(m, 1H, Olefine), 5.69(d,J=7.1 Hz, 1H, H2β0), 5.11(m, 2H, olefine), 4.97(d, J=7.7, 1H, H5),4.50(d, J=8.2 Hz, 1H, NH), 4.43(m, 1H, H2'), 4.41(m, 1H, H7), 4.31(d,J=7.8 Hz, 1H, H20α), 4.20(d, J=7.8 Hz, 1H, H20β), 3.80(d, J=7.1 Hz, 1H,H3), 3.75(ddd, J=8.8, 8.8, 1.8 Hz, 1H, H3'), 3.34(d, J=6.6 Hz, 1H,2'OH), 2.54(m, 1H, H6α), 2.50(d, J=3.9 Hz, 1H, 7OH), 2.44(s, 3H, 4Ac),2.35(m, 2H, H14), 2.27(s, 3H, 10Ac), 2.25(br s, 3H, Me18), 1.98(m, 1H,CH3CHCH3 isopropyl) 1.88 (m, 1H, H6β), 1.84(s, 3H, Me19), 1.27(s, 3H,Me17), 1.15(s, 3H, Me16), 1.11(d, J=6.6 Hz, 3H, Me isopropyl), 1.03(d,J=6.6 Hz, 3H, Me isopropyl).

EXAMPLE 75 ##STR98## Preparation of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(benzyloxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.071 mmol) in0.8 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.00 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-benzyloxycarbonyl-3-triethylsilyloxy-4-isopropyl azetidin-2-one(81.0 mg, 0.21 mmol) in 0.8 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 61.4 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(benzyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 61.4 mg (0.057 mmol) of the mixture obtained from theprevious reaction in 3.5 mL of acetonitrile and 0.17 mL of pyridine at0° C. was added 0.48 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 50.3 mg of material which was purified by flashchromatography to give 32.7 mg (68%) of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(benzyloxycarbonyl) taxol, whichwas recrystallized from methanol/water.

m.p.143-145° C.; [α]²⁵ Na -56.1° (c 0.002, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.1 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 7.23-7.21 (m,3H, benzyl), 7.10-7.05(m, 2H, benzyl), 6.28(s, 1H, H10), 6.22 (dd,J=7.7, 7.7 Hz, 1H, H13), 5.69(d, J=7.1 Hz, 1H, H2β), 5.03(d, J=12.3 Hz,1H, benzyl), 4.97(d, J=7.7, 1H, H5), 4.89(d, J=12.3 Hz, 1H, benzyl),4.81(d, J=8.2 Hz, 1H, NH), 4.53(m, 1H, H2'), 4.41(m, 1H, H7), 4.30(d,J=7.8 Hz, 1H, H20α), 4.19(d, J=7.8 Hz, 1H, H20β), 3.80(d, J=7.1 Hz, 1H,H3), 3.68(ddd, J=8.8, 8.8, 3.3 Hz, 1H, H3'), 3.21 (d, J=6.6 Hz, 1H,2'OH), 2.53(m, 1H, H6α), 2.48(d, J=3.9 Hz, 1H, 7OH), 2.42(s, 3H, 4Ac),2.38(m, 2H, H14), 2.23(s, 3H, 10Ac), 2.16(br s, 3H, Me18), 1.96(m, 1H,CH₃ CHCH₃ isopropyl) 1.89(m, 1H, H6β), 1.86(s, 3H, Me19), 1.23(s, 3H,Me17), 1.16 (s, 3H, Me16), 1.08(d, J=6.6 Hz, 3H, Me isopropyl), 1.03 (d,J=6.6 Hz, 3H, Me isopropyl).

EXAMPLE 76 ##STR99## Preparation ofN-debenzoyl-N-(3-butynyloxycarbonyl)-3'-desphenyl-3'-isopropyl Taxol

To a solution of 7-triethylsilyl baccatin III (100.0 mg, 0.123 mmol) in1.5 mL of THF at -45° C. was added dropwise 0.14 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(3-butynyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isopropylazetidin-2-one (109.6 mg, 0.369 mmol) in 1.0 mL of THF was addeddropwise to the mixture. The solution was warmed to 0° C. and kept atthat temperature for 1 h before 1.0 mL of a 10% solution of AcOH in THFwas added. The mixture was partitioned between saturated aqueous NaHCO₃and 60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give116.7 mg of a mixture containing(2'R,3'S)-2'-O-(2-methoxy-2-propoxy)-7-triethylsilyl-N-debenzoyl-N-(3-butynyloxycarbonyl)-3'-desphenyl-3'-isopropyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 116.7 mg (0.12 mmol) of the mixture obtained from theprevious reaction in 8.0 mL of acetonitrile and 0.5 mL of pyridine at 0°C. was added 1.30 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 91.2 mg of material which was purified by flashchromatography to give 68.7 mg (72%) ofN-debenzoyl-N-(3-butynyloxycarbonyl)-3'-desphenyl-3'-isopropyl taxol,which was recrystallized from methanol/water.

m.p.140-143.5° C.; [α]²⁵ Na -56.0° (c 0.0019, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.2 Hz, 2H, benzoate ortho),7.63(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 6.30(s, 1H,H10), 6.28(dd, J=8.1, 8.1 Hz, 1H, H13), 5.68(d, J=6.9 Hz, 1H, H2β),4.95(d, J=7.8 Hz, 1H, H5), 4.93(s, 1H, butylnyloxy), 4.50(d, J=8.2 Hz,1H, NH), 4.42(m, 1H, H2'), 4.40(m, 1H, H7), 4.32(d, J=8.4 Hz, 1H, H20α),4.20(d, J=8.4 Hz, 1H, H20β), 4.00(t, J=6.6 Hz, 2H, butylnyloxy), 3.80(d,J=7.2 Hz, 1H, H3), 3.75(ddd, J=8.7, 8.7, 1.8 Hz, 1H, H3'), 3.30(d, J=6.6Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.50(d, J=3.9 Hz, 1H, 7OH), 2.44(s, 3H,4Ac), 2.35(m, 2H, H14), 2.27(s, 3H, 10Ac), 2.25(br s, 3H, Me18), 1.98(m,1H, CH3CHCH3 isopropyl) 1.88 (m, 1H, H6β), 1.84(s, 3H, Me19), 1.75(s,1H, 1OH), 1.27(s, 3H, Me17), 1.15(s, 3H, Me16), l.1l(d, J=6.6 Hz, 3H, Meisopropyl), 1.03(d, J=6.6 Hz, 3H, Me isopropyl), 0.88(t, J=6.6 Hz, 3H,butylnyloxy).

EXAMPLE 77 ##STR100## Preparation of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(crotyloxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (100.0 mg, 0.142 mmol) in1.0 mL of THF at -45° C. was added dropwise 0.16 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(3'-crotyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-(isopropyl)-azetidin-2-one(128.2 mg, 0.43 mmol) in 1.0 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1.0 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 128.9 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isopropyl-7-triethylsilyl-N-debenzoyl-N-(crotyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 128.9 mg (0.116 mmol) of the mixture obtained from theprevious reaction in 9.0 mL of acetonitrile and 0.5 mL of pyridine at 0°C. was added 1.30 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 131.4 mg of material which was purified by flashchromatography to give 71.7 mg (76%) of3'-desphenyl-3'-(isopropyl)-N-debenzoyl-N-(crotyloxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p.146-148° C.; [α]²⁵ Na -56.2° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.2 Hz, 2H, benzoate ortho),7.63(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.28(s, 1H,H10), 6.21(dd, J=8.1, 8.1 Hz, 1H, H13), 5.68(d, J=6.9 Hz, 1H, H2β),5.62(m, 1H, crotyl), 5.44(m, 1H, crotyl), 4.96(d, J=7.8 Hz, 1H, H5),4.51(d, J=8.2 Hz, 1H, NH), 4.42(m, 1H, H2'), 4.40(m, 1H, H7), 4.35(m,2H, crotyl), 4.28(d, J=8.4 Hz, 1H, H20α), 4.20(d, J=8.4 Hz, 1H, H20β),3.88(d, J=7.2 Hz, 1H, H3), 3.73(ddd, J=8.7, 8.7, 1.8 Hz, 1H, H3'),3.34(d, J=6.6 Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.52(d, J=3.9 Hz, 1H,7OH), 2.32(s, 3H, 4Ac), 2.28(m, 2H, H14), 2.24(s, 3H, 10Ac), 2.19(br s,3H, Me18), 1.98(m, 1H, CH3CHCH3 isopropyl) 1.88 (m, 1H, H6β), 1.72(s,3H, Me19), 1.69(s, 1H, 1OH), 1.61(d, J=6.6 Hz, 3H, crotyl), 1.27(s, 3H,Me17), 1.15(s, 3H, Me16), 1.11(d, J=6.6 Hz, 3H, Me isopropyl), 1.03(d,J=6.6 Hz, 3H, Me isopropyl).

EXAMPLE 78 ##STR101## Preparation of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(cyclohexyloxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.071 mmol) in0.8 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.00 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(cyclohexyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isopropylazetidin-2-one(73.0 mg, 0.22 mmol) in 0.8 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NAHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 62.3 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isopropyl-7-triethylsilyl-N-debenzoyl-N-(cyclohexyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 62.3 mg (0.055 mmol) of the mixture obtained from theprevious reaction in 6.5 mL of acetonitrile and 0.30 mL of pyridine at0° C. was added 0.65 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 55.6 mg of material which was purified by flashchromatography to give 32.9 mg (73%) of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(cyclohexyloxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p.148-150° C.; [α]²⁵ Na -57.4° (c 0.0024, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.2 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.29(s, 1H,H10), 6.25 (dd, J=7.8, 7.8 Hz, 1H, H13), 5.49(d, J=7.2 Hz, 1H, H2β),4.89(d, J=7.8, 1H, H5), 4.73(d, J=8.1 Hz, 1H, NH), 4.55(m, 1H, H2'),4.43(m, 1H, H7), 4.39(m, 1H, cyclohexyloxy), 4.34(d, J=7.8 Hz, 1H,H20α), 4.20(d, J=7.8 Hz, 1H, H20β), 3.82(d, J=7.1 Hz, 1H, H3), 3.68(ddd,J=8.8, 8.8, 3.3 Hz, 1H, H3'), 3.24 (d, J=6.6 Hz, 1H, 2'OH), 2.52(m, 1H,H6α), 2.47(d, J=3.6 Hz, 1H, 7OH), 2.39(s, 3H, 4Ac), 2.36(m, 2H, H14),2.22(s, 3H, 10Ac), 2.15(br s, 3H, Me18), 1.96(m, 1H, CH₃ CHCH₃isopropyl), 1.89((m, 1H, H6β), 1.88(s, 3H, Me19), 1.72(m, 2H,cyclohexyloxy), 1.53(m, 4H, cyclohexyloxy), 1.35(m, 2H, cyclohexyloxy),1.25(s, 3H, Me17), 1.15(s, 3H, Me16), 1.06(d, J=6.6 Hz, 3H, Meisopropyl), 1.02(d, J=6.6 Hz, 3H, Me isopropyl).

EXAMPLE 79 ##STR102## Preparation of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(2-methoxyethoxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (50.0 mg, 0.71 mmol) in0.7 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(2-methoxyethoxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isopropylazetidin-2-one(75.1 mg, 0.21 mmol) in 0.7 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1.0 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 60.2 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isopropyl-7-triethylsilyl-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 60.2 mg (0.58 mmol) of the mixture obtained from theprevious reaction in 5.0 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.65 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 48.2 mg of material which was purified by flashchromatography to give 36.1 mg (76%) of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(2-methoxyethoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p.151-153° C.; [α]²⁵ Na -56.0° (c 0.0018, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.08(d, J=7.2 Hz, 2H, benzoate ortho),7.62(m, 1H, benzoate para), 7.49(m, 2H, benzoate meta), 6.31(s, 1H,H10), 5.91(dd, J=8.1, 8.1 Hz, 1H, H13), 5.64(d, J=6.9 Hz, 1H, H2β),4.97(d, J=7.8 Hz, 1H, H5), 4.58(d, J=8.2 Hz, 1H, NH), 4.46 (m, 1H, H2'),4.38(m, 1H, H7), 4.34(d, J=8.4 Hz, 1H, H20α), 4.28(t, J=4.5 Hz, 2H,MeO-CH₂ CH₂ O), 4.14(d, J=8.4 Hz, 1H, H20β), 3.86(d, J=7.2 Hz, 1H, H3),3.65(t, J=4.5 Hz, 2H, MeO--CH₂ CH₂ O), 3.63(ddd, J=8.7, 8.7, 1.8 Hz, 1H,H3'), 3.41(s, 3H, MeO--), 3.38(d, J=6.6 Hz, 1H, 2'CH), 2.56(m, 1H, H6α),2.47(d, J=3.9 Hz, 1H, 7OH), 2.39(s, 3H, 4Ac), 2.35(m, 2H, H14), 2.26(s,3H, 10Ac), 2.24(br s, 3H, Me18), 1.96(m, 1H, CH3CHCH3 isopropyl) 1.88(m,1H, H6β), 1.86(s, 3H, Me19), 1.75(s, 1H, 1OH), 1.27(s, 3H, Me17),1.15(s, 3H, Me16), 1.11 (d, J=6.6 Hz, 3H, Me isopropyl), 1.03(d, J=6.6Hz, 3H, Me isopropyl).

EXAMPLE 80 ##STR103## Preparation of3'-desphenyl-3'-isopropyl-N-debenzoyl-N-(neopentyloxycarbonyl) Taxol

To a solution of 7-triethylsilyl baccatin III (100.0 mg, 0.142 mmol) in1.4 mL of THF at -45° C. was added dropwise 0.16 mL of a 1.00 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(neopenthyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-isopropylazetidin-2-one(135.5 mg, 0.43 mmol) in 1.4 mL of THF was added dropwise to themixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 123.1 mg of amixture containing(2'R,3'S)-2'-(2-methoxy-2-propoxy)-3'-desphenyl-3'-isopropyl-7-triethylsilyl-N-debenzoyl-N-(neopentyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 123.1 mg (0.109 mmol) of the mixture obtained from theprevious reaction in 9.0 mL of acetonitrile and 0.48 mL of pyridine at0° C. was added 1.25 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 114.7 mg of material which was purified by flashchromatography to give 68.4 mg (81%) of3'-desphenyl-3'-(isopropyl)-N-debenzoyl-N-(neopentyloxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 145-147° C; [α]²⁵ _(Na) -56.8° (c 0.0023, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15 (d, J=7.2 Hz, 2H, benzoate ortho), 7.60(m, 1H, benzoate para), 7.50 (m, 2H, benzoate meta), 6.32 (s, 1H, H10),6.24 (dd, J=7.8, 7,8 Hz, 1H, H13), 5.57 (d, J=7.2 Hz, 1H, H2β), 4.89 (d,J=7.8, 1H, H5), 4.74 (d, J=8.2 Hz, 1H, NH), 4.52 (m, 1H, H2'), 4.39 (m,1H, H7), 4.32 (d, J=7.8 Hz, 1H, H20α), 4.17 (d, J=7.8 Hz, 1H, H20β),3.78 (s, 2H, neopenthyloxy), 3.69 (d, J=7.1 Hz, 1H, H3), 3.65 (ddd,J=8.1, 8.1, 3.3 Hz, 1H, H3'), 3.20 (d, J=6.6 Hz, 1H, 2'OH), 2.53 (m, 1H,H6α), 2.46 (d, J=3.6 Hz, 1H, 70H), 2.38 (s, 3H, 4Ac), 2.36 (m, 2H, H14),2.22 (s, 3H, 10Ac), 2.14 (br s, 3H, Me18), 1.96 (m, 1H, CH₃ CHCH₃isopropyl) 1.87 ((m, 1H, H6β), 1.83 (s, 3H, Me19), 1.21(s, 9H, Meneopenthyloxy), 1.19 (s, 3H, Me17), 1.14 (s, 3H, Me16), 1.06 (d, J=6.6Hz, 3H, Me isopropyl), 1.03 (d, J=6.6 Hz, 3H, Me isopropyl).

EXAMPLE 81 ##STR104## Preparation of3'-desphenyl-3'-isopropyl-N-desbenzoyl-N-(trimethylsilylmethyloxycarbonyl)taxol

To a solution of 7-O-triethylsilyl baccatin III (50.0 mg, 0.71 mmol) in0.7 mL of THF at -45° C. was added dropwise 0.08 mL of a 1.0 M solutionof LiN(SiMe₃)₂ in hexane. After 0.5 h at -45° C., a solution ofcis-1-(3'-trimethylsilylmethyloxycarbonyl)-3-(2-methoxyisopropoxy)-4-(isopropyl)azetidin-2-one(58.0 mg, 0.21 mmol) in 0.7 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1.0 mL of a 10% solution of AcOH in THF was added. The mixturewas partitioned between saturated aqueous NaHCO, and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 66.4 mg of amixture containing(2'R,3'S)-2'-O-(2-methoxyisopropyl)-7-O-triethylsilyl-3'-desphenyl-3'-isopropyl-N-desbenzoyl-N-(trimethylsilylmethyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 66.4 mg (0.58 mmol) of the mixture obtained from theprevious reaction in 6.0 mL of acetonitrile and 0.35 mL of pyridine at0° C. was added 0.72 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 54.4 mg of material which was purified by flashchromatography to give 35.4 mg (72%) of3'-desphenyl-3'-isopropyl-N-desbenzoyl-N-(trimethylsilylmethyloxycarbonyl)taxol, which was recrystallized from methanol/water.

m.p. 149-150° C.; [α]²⁵ _(Na) -55.7° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.2 Hz, 2H, benzoate ortho),7.62(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.30(s, 1H,H10), 6.28(dd, J=8.1, 8.1 Hz, 1H, H13), 5.68(d, J=6.9 Hz, 1H, H2p),4.95(d, J=7.8 Hz, 1H, H5), 4.77(d, J=8.2 Hz, 1H, NH), 4.48(m, 1H, H2'),4.40(m, 1H, H7), 4.32(d, J=8.4 Hz, 1H, H20α), 4.20(d, J=8.4 Hz, 1H,H20β), 3.80(d, J=7.2 Hz, 1H, H3), 3.75(ddd, J=8.7, 8.7, 1.8 Hz, 1H,H3'), 3.61(d, J=14.28 Hz, 1H, CH₂ TMS), 3.51(d, J=14.28 Hz, 1H, CH₂TMS), 3.40(d, J=6.6 Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.50(d, J=3.9 Hz,1H, 70H), 2.44(s, 3H, 4Ac), 2.35(m, 2H, H14), 2.25(s, 3H, 10Ac), 2.03(brs, 3H, Me18), 1.98(m, 1H, CH3CHCH3 isopropyl) 1.84 (m, 1H, H6β), 1.73(s,3H, Me19), 1.67(s, 1H, 1OH), 1.27(s, 3H, Me17), 1.15(s, 3H, Me16),1.11(d, J=6.6 Hz, 3H, Me isopropyl), 1.03(d, J=6.6 Hz, 3H, Meisopropyl), -0.03(s, 9H, Me₃ Si--).

EXAMPLE 82 ##STR105## Preparation of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(ethoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 2mL of THF at -45° C. was added dropwise 0.157 mL of a 1.OM solution of(TMS)2NLi in THF. After 1 h at -45° C., a solution ofcis-l-(ethoxycarbonyl)-3-triethylsilyloxy-4-cyclopropyl azetidin-2-one(225 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO, and 60/40 ethyl acetate/ hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 125 mg of a mixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(ethoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 125 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 93 mg of material which was purified by flashchromatography to give 82 mg (85%) of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(ethoxycarbonyl) taxol, whichwas recrystallized from ether/hexane.

m.p. 140-142° C.; [α]²⁵ _(Na) -65.0° (c 0.08, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.10 (d, J=7.2 Hz, 2H, benzoate ortho), 7.60(m, 1H, benzoate, para), 7.49 (t, J=7.2 Hz, 2H, benzoate, meta), 6.29(s, 1H, H10), 6.22 (br t, J=8.7 Hz, 1H, H13), 5.66 (d, J=6.9 Hz, 1H,H2β), 5.08 (d, J=9.3 Hz, 1H, NH), 4.95 (dd, J=9.3, 1.5 Hz, 1H, H5), 4.43(dd, J=6.0, 2.1 Hz,1H, H2'), 4.40 (m, 1H, H7), 4.30 (d, J=8.1 Hz, 1H,H20α), 4.17 (d, J=8.1 Hz, 1H, H20β), 3.96 (q, J=7.2 Hz, 2H, OCH2), 3.79(d, J=6.9 Hz, 1H, H3), 3.47 (d, J=6.0 Hz, 1H, 2'OH), 3.35 (dt, J=9.3,2.1 Hz, 1H, H3'), 2.52 (m, 2H, H6α, 70H), 2.36 (s, 3H, 4Ac), 2.23 (s,3H, 10Ac), 1.88 (s, 3H, Me18), 1.67 (s, 3H, Me19), 1.47 (m, 2H, CH2),1.24 (s, 3H, Me17), 1.14 (s, 3H, Me16), 1.11 (t, J=7.2 Hz, Me), 0.64 (m,2H, cyclopropyl), 0.47 (m, 1H, cyclopropyl), 0.29 (m, 1H, cyclopropyl).EXAMPLE 83 ##STR106##

Preparation of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution of(TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-cyclopropylazetidin-2-one(170 mg, 0.5 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was gradually warmed to 0° C. during 6h before 1 mL of a 10%solution of AcOH in THF was added. The mixture was partitioned betweensaturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane. Evaporation ofthe organic layer gave a residue which was purified by filtrationthrough silica gel to give 140 mg of a mixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 140 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 109 mg of material which was purified by flashchromatography to give 106 mg (97%) of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from ether/hexane.

m.p. 167-169° C.; [α]²⁵ _(Na) -74.0° (c 0.1, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.10 (d, J=7.5 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.49 (t, J=7.5 Hz, 2H, benzoate, meta), 6.30(s, 1H, H10), 6.16 (br t, J=8.7 Hz, 1H, H13), 5.67 (d, J=7.2 Hz, 1H,H2β), 4.96 (dd, J=9.3, 1.5 Hz, 1H, H5), 4.91 (d, J=9.3 Hz, 1H, NH), 4.41(m, 1H, H7), 4.39 (dd, J=6.6, 1.8 Hz, 1H, H2'), 4.31 (d, J=8.1 Hz, 1H,H20α), 4.16 (d, J=8.1 Hz, 1H, H20β), 3.79 (d, J=7.2 Hz, 1H, H3), 3.37(d, J=6.6 Hz, 1H, 2'OH), 3.29 (dt, J=9.3, 1.8 Hz, 1H, H3'), 2.55 (m, 1H,H6α), 2.50 (d, J=3.9 Hz, 1H, 70H), 2.35 (s, 3H, 4Ac), 2.30 (br d, J=9.3Hz, 2H, H14), 2.23 (s, 3H, 10Ac), 1.89 (d, J=0.9 Hz, 3H, Me18), 1.74 (s,1H, 1OH), 1.66 (s, 3H, Me19), 1.31 (s, 9H, t-Bu), 1.24 (s, 3H, Me17),1.14 (s, 3H, Me16), 0.63 (m, 2H, cyclopropyl), 0.46 (m, 1H,cyclopropyl), 0.25 (m, 1H, cyclopropyl).

EXAMPLE 84 ##STR107## Preparation of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(n-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in1.5 mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0M solutionof (TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(n-butoxycarbonyl)-3-triethylsilyloxy-4-cyclopropyl azetidin-2-one(170 mg, 0.5 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was gradually warmed to 0° C. during 6h before 1 mL of a 10%solution of AcOH in THF was added. The mixture was partitioned betweensaturated aqueous NaHCO₃ and 60/40 ethyl acetate/ hexane. Evaporation ofthe organic layer gave a residue which was purified by filtrationthrough silica gel to give 145 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(n-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 145 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 108 mg of material which was purified by flashchromatography to give 98 mg (87%) of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(n-butoxycarbonyl) taxol,which was recrystallized from ether/hexane.

m.p. 132-134° C.; [α]²⁵ _(Na) -64.0° (c 0.175, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (d, J=7.8 Hz, 2H, benzoate ortho), 7.60(m, 1H, benzoate, para), 7.49 (t, J=7.8 Hz, 2H, benzoate, meta), 6.29(s, 1H, H10), 6.22 (br t, J=9.3 Hz, 1H, H13), 5.66 (d, J=6.9 Hz, 1H,H2β), 5.04 (d, J=9.3 Hz, 1H, NH), 4.95 (dd, J=9.6, 1.8 Hz, 1H, H5), 4.43(dd, J=5.4, 2.1 Hz,1H, H2'), 4.40 (m, 1H, H7), 4.30 (d, J=8.7 Hz, 1H,H20α), 4.17 (d, J=8.7 Hz, 1H, H20β), 3.89 (m, 2H, OCH2), 3.79 (d, J=6.9Hz, 1H, H3), 3.43 (d, J=5.4 Hz, 1H, 2'OH), 3.36 (dt, J=9.3, 2.1 Hz, 1H,H3'), 2.55 (m, 1H, H6α), 2.49 (d, J=4.5 Hz, 1H, 70H), 2.36 (s, 3H, 4Ac),2.24 (s, 3H, 10Ac), 1.88 (s, 3H, Me18), 1.75 (s, 1H, 1OH), 1.67 (s, 3H,Me19), 1.47 (m, 2H, CH2), 1.26 (s, 3H, Me17), 1.23 (m, 2H, CH2), 1.14(s, 3H, Me16), 0.82 (t, J=7.2 Hz, 3H, Me), 0.64 (m, 2H, cyclopropyl),0.47 (m, 1H, cyclopropyl), 0.29 (m, 1H, cyclopropyl).

EXAMPLE 85 ##STR108## Preparation of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(isobutoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 2mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0M solution of(TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(isobutoxycarbonyl)-3-triethylsilyloxy-4-cyclopropylazetidin-2-one(244 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 145 mg of a mixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(isobutoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 145 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 95 mg of material which was purified by flashchromatography to give 87 mg (85%) of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(isobutoxycarbonyl) taxol,which was recrystallized from ether/hexane.

m.p. 130-132° C.; [α]²⁵ _(Na) -64.0° (c 0.15, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=7.2 Hz, 2H, benzoate, meta), 6.29(s, 1H, H10), 6.22 (br t, J=8.7 Hz, 1H, H13), 5.67 (d, J=7.2 Hz, 1H,H2β), 5.05 (d, J=9.6 Hz, 1H, NH), 4.96 (dd, J=9.3, 1.8 Hz, 1H, H5), 4.43(dd, J=5.4, 2.1 Hz, 1 H, H2'), 4.41 (m, 1H, H7), 4.30 (d, J=8.4 Hz, 1H,H20α), 4.17 (d, J=8.4 Hz, 1H, H20β), 3.79 (d, J=7.2 Hz, 1H, H3), 3.67(m, 2H, i-Bu), 3.39 (d, J=5.4 Hz, 1H, 2'OH), 3.37 (dt, J=9.3, 2.1 Hz,1H, H3'), 2.55 (m, 1H, H6α), 2.48 (d, J=3.9 Hz, 1H, 70H), 2.37 (s, 3H,4Ac), 2.24 (s, 3H, 10Ac), 1.88 (s, 3H, Me18), 1.67 (s, 3H, Me19), 1.25(s, 3H, Me17), 1.14 (s, 3H, Me16), 0.80 (d, J=6.6 Hz, 3H, Me), 0.76 (d,J=6.6 Hz, 3H, Me), 0.64 (m, 2H, cyclopropyl), 0.48 (m, 1H, cyclopropyl),0.29 (m, 1H, cyclopropyl).

EXAMPLE 86 ##STR109## Preparation of3'-desphenyl-3'-cyclopropyl-N-desbenzoyl-N-(isopropoxycarbonyl) taxol

To a solution of 7-O-triethylsilyl baccatin III (100 mg, 0.143 mmol) in2 mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0M solution of(TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(isopropoxycarbonyl)-3-triethylsilyloxy-4-cyclopropylazetidin-2-one(145 mg, 0.429 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 9h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 145 mg of a mixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-cyclopropyl-N-desbenzoyl-N-(isopropoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 145 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 111 mg of material which was purified by flashchromatography to give 95 mg (84%) of3'-desphenyl-3'-cyclopropyl-N-desbenzoyl-N-(isopropoxycarbonyl) taxol,which was recrystallized from ether/hexane.

m.p. 142-144° C.; [α]²⁵ _(Na) -77.06° (c 0.17, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.49 (t, J=7.2 Hz, 2H, benzoate, meta), 6.29(s, 1H, H10), 6.20 (br t, J=9.0 Hz, 1H, H13), 5.67 (d, J=7.2 Hz, 1H,H2β), 4.97 (d, J=9.6 Hz, 1H, NH), 4.96 (dd, J=9.3, 1.8 Hz, 1H, H5), 4.71(m, 1H, isopropyl), 4.42 (m, 2H, H7 and H2'), 4.31 (d, J=8.4 Hz, 1H,H20α), 4.17 (d, J=8.4 Hz, 1H, H20β), 3.79 (d, J=7.2 Hz, 1H, H3), 3.39(d, J=6.0 Hz, 1H, 2'OH), 3.35 (dt, J=9.3, 2.1 Hz, 1H, H3'), 2.55 (m, 1H,H6α), 2.48 (d, J=3.9 Hz, 1H, 70H), 2.36 (s, 3H, 4Ac), 2.24 (s, 3H,10Ac), 1.88 (s, 3H, Me18), 1.67 (s, 3H, Me19), 1.25 (s, 3H, Me17), 1.14(s, 3H, Me16), 1.14 (d, J=6.0 Hz, 3H, isopropyl), 1.05 (d, J=6.0 Hz, 3H,isopropyl), 0.64 (m, 2H, cyclopropyl), 0.47 (m, 1H, cyclopropyl), 0.28(m, 1H, cyclopropyl).

EXAMPLE 87 ##STR110## Preparation of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(allyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 2mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0M solution of(TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(allyloxycarbonyl)-3-triethylsilyloxy-4-cyclopropyl azetidin-2-one(220 mg, 0.672 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 6h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/ hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 125 mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(allyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 120 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 87 mg of material which was purified by flashchromatography to give 79 mg (85%) of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(allyloxycarbonyl) taxol,which was recrystallized from ether/hexane.

m.p. 138-140 ° C; [α]²⁵ _(Na) -68.2° (c 0.085, CHCl₃).

¹ H gNMR (CDCl₃, 300 MHz) δ 8.12 (d, J=7.2 Hz, 2H, benzoate ortho), 7.61(m, 1H, benzoate, para), 7.50 (t, J=7.2 Hz, 2H, benzoate, meta), 6.29(s, 1H, H10), 6.22 (br t, J=8.4 Hz, 1H, H13), 5.78 (m, 1H, allyl), 5.67(d, J=7.2 Hz, 1H, H2β), 5.14 (m, 2H, allyl), 5.09 (d, J=9.6 Hz, 1H, NH),4.96 (dd, J=9.3, 2.4 Hz, 1H, H5), 4.43 (m, 4H, OCH2, H7 and H2,), 4.30(d, J=8.4 Hz, 1H, H20α), 4.18 (d, J=8.4 Hz, 1H, H20β), 3.79 (d, J=6.9Hz, 1H, H3), 3.39 (dt, J=9.6, 1.8 Hz, 1H, H3'), 3.35(d, J=5.4 Hz, 1H,2'OH), 2.55 (m, 1H, H6α), 2.45 (d, J=3.9 Hz, 1H, 70H), 2.36 (s, 3H,4Ac), 2.24 (s, 3H, 10Ac), 1.88 (s, 3H, Me18), 1.68 (s, 3H, Me19), 1.26(s, 3H, Me17), 1.14 (s, 3H, Me16), 0.64 (m, 2H, cyclopropyl), 0.48 (m,1H, cyclopropyl), 0.29 (m, 1H, cyclopropyl).

EXAMPLE 88 ##STR111## Preparation of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(benzyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 2mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0M solution of(TMS)₂ NLi in THF. After 1 h at -45° C., a solution ofcis-1-(benzyloxycarbonyl)-3-triethylsilyloxy-4-cyclopropylazetidin-2-one(264 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was gradually warmed to 0° C. during 10 h before 1 mL of a10% solution of AcOH in THF was added. The mixture was partitionedbetween saturated aqueous NaHCO₃ and 60/40 ethyl acetate/hexane.Evaporation of the organic layer gave a residue which was purified byfiltration through silica gel to give 144 mg of a mixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(benzyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 144 mg of the mixture obtained from the previousreaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 109 mg of material which was purified by flashchromatography to give 97 mg (86%) of3'-desphenyl-3'-cyclopropyl-N-debenzoyl-N-(benzyloxycarbonyl) taxol,which was recrystallized from ether/hexane.

m.p. 128-130° C.; [α]²⁵ _(Na) -64.21° (c 0.19, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) 8 8.11 (d, J=7.2 Hz, 2H, benzoate ortho), 7.60(m, 1H, benzoate, para), 7.49 (t, J=7.2 Hz, 2H, benzoate, meta), 7.25(m, 3H, benzyl), 7.14 (m, 2H, benzyl), 6.26 (s, 1H, H10), 6.18 (br t,J=8.7 Hz, 1H, H13), 5.64 (d, J=7.2 Hz, 1H, H2β), 5.24 (d, J=9.3 Hz, 1H,NH), 5.01 (d, J=12.6 Hz, 1H, benzyl), 4.94 (dd, J=9.3, 1.5 Hz, 1H, H5),4.91 (d, J=12.6 Hz, 1H, benzyl), 4.44 (br s, 1 H, H2'), 4.40 (dd,J=11.1, 6,6 Hz, 1H, H7), 4.28 (d, J=8.4 Hz, 1H, H20α), 4.18 (d, J=8.4Hz, 1H, H20β), 3.75 (d, J=7.2 Hz, 1H, H3), 3.44 (br s, 1H, 2'OH), 3.41(dt, J=9.3, 2.1 Hz, 1H, H3'), 2.53 (m, 1H, H6α), 2.36 (s, 3H, 4Ac), 2.23(s, 3H, 10Ac), 1.83 (s, 3H, Me18), 1.67 (s, 3H, Me19), 1.21 (s, 3H,Me17), 1.12 (s, 3H, Me16), 0.64 (m, 2H, cyclopropyl), 0.47 (m, 1H,cyclopropyl), 0.29 (m, 1H, cyclopropyl).

EXAMPLE 89 ##STR112## Preparation of3'-desphenyl-3'-t-butyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (120 mg, 0.171 mmol) in1.2 mL of THF at -45° C. was added dropwise 0.188 mL of a 1.00 Msolution of lithium bis(trimethylsilyl)amide in THF. After 0.5 h at -45°C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-t-butylazetidin-2-one (303mg, 0.855 mmol) in 1.2 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 180.4 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-t-butyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 180.4 mg (0.171 mmol) of the mixture obtained from theprevious reaction in 11 mL of acetonitrile and 0.55 mL of pyridine at 0°C. was added 1.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 141 mg of material which was purified by flashchromatography to give 133 mg (92%) of3'-desphenyl-3'-t-butyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol, whichwas recrystallized from methanol/water.

m.p. 158-159° C.; [α]²⁵ _(Na) -44.0° (c 0.0055, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=7.7 Hz, 2H, benzoate, ortho),7.61-7.47(m, 3H, aromatic), 6.29(s, 1H, H10), 6.18(dd, J=8.9, 8.9 Hz,1H, H13), 5.68(d, J=7.1 Hz, 1H, H2β), 4.97 (d, J=9.3 Hz, 1H, H5),4.87(d, J=10.4 Hz, 1H, NH), 4.56 (d, J=5.5 Hz, 1H, H3'), 4.41(m, 1H,H7), 4.32(d, J=8.8 Hz, 1H, H20α), 4.17(d, J=8.8 Hz, H20β),3.79(m2H,H2',H3), 3.07(d, J=5 Hz, 1H, 2'OH), 2.61(m, 1H, H6α), 2.45(d, J=4.5Hz, 1H, 70H), 2.41(s, 3H, 4Ac), 2.35(m, 2H, H14), 2.24 (s, 3H,10Ac),1.95 (m, 1H, H6β), 1.88(br s, 3H, Me18), 1.68(s, 1H, 10H), 1.67(s,3H, Me19), 1.30(s, 9H, t-butoxyl), 1.26(s, 3H, Me17), 1.14(s, 3H, Me16),1.04(s, 9H t-butyl).

EXAMPLE 90 ##STR113## Preparation of3'-desphenyl-3'-cyclobutyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (120 mg, 0.171 mmol) in1.2 mL of THF at -45° C. was added dropwise 0.188 mL of a 1.00 Msolution of lithium bis(trimethylsilyl)amide in THF. After 0.5 h at -45°C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-cyclobutylazetidin-2-one(303 mg, 0.855 mmol) in 1.2 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 180.5 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclobutyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 180.5 mg (0.171 mmol) of the mixture obtained from theprevious reaction in 11 mL of acetonitrile and 0.55 mL of pyridine at 0°C. was added 1.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 141 mg of material which was purified by flashchromatography to give 133 mg (92%) of3'-desphenyl-3'-cyclobutyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol, whichwas recrystallized from methanol/water.

m.p. 168-169° C.; [α]²⁵ _(Na) -41.0° (c 0.006, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=7.7 Hz, 2H, benzoate, ortho),7.62-7.48(m, 3H, aromatic), 6.30(s, 1H, H10), 6.18(dd, J=8.9, 8.9 Hz,1H, H13), 5.68(d, J=7.1 Hz, 1H, H2β), 4.98(d, J=9.9 Hz, 1H, H5), 4.57(d,J=9.3 Hz, 1H, NH),4.42(m, 1H, H7), 4.33(d, J=8.8 Hz, 1H, H20α),4.22-4.16(m, 2H, H20β, H2'), 3.94(dd, J=9.3, 6.0 Hz, 1H, H3'), 3.80(d,J=6.6 Hz, 1H, H3), 3.13(d, J=6 Hz, 1H, 2'OH), 2.60(m, 1H, H6α), 2.45(d,J=4.5 Hz, 1H, 70H), 2.43(s, 3H, 4Ac), 2.35(m, 2H, H14), 2.23 (s, 3H,10Ac), 1.95 (m, 1H, H6β), 1.88(br s, 3H, Me18), 1.80-1.78 (m,7H,cyclobutyl), 1.77(s, 1H, 1OH), (1.67, s, 3H, Me19), 1.30 (s, 9H,t-butoxy), 1.25(s, 3H, Me17), 1.15(s, 3H, Me16).

EXAMPLE 91 ##STR114## Preparation of3'-desphenyl-3'-cyclopentyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (120 mg, 0.171 mmol) in1.2 mL of THF at -45° C. was added dropwise 0.188 mL of a 1.00 Msolution of lithium bis(trimethylsilyl)amide in THF. After 0.5 h at -45°C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-cyclopentylazetidin-2 -one(316 mg, 0.855 mmol) in 1.2 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 183 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclopentyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 183mg (0.171 mmol) of the mixture obtained from theprevious reaction in 11 mL of acetonitrile and 0.55 mL of pyridine at 0°C. was added 1.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 144 mg of material which was purified by flashchromatography to give 136 mg (94%) of3'-desphenyl-3'-cyclopentyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 164-165° C.; [α]²⁵ _(Na) -37.0° (c 0.0055, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (d, J=8.2 Hz, 2H, benzoate, ortho),7.61-7.47(m, 3H, aromatic), 6.30(s, 1H, H10), 6.20(dd, J=8.9, 8.9 Hz,1H, H13), 5.67(d, J=7.1 Hz, 1H, H2β), 4.95(d, J=7.7 Hz, 1H, H5), 4.72(d,J=9.3 Hz, 1H, NH)4.40(m, 1H, H7), 4.35-4.16(m, 3H, H20's, H3'), 3.79(m,2H, H3, H2'), 3.23(d, J=6 Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.40(s, 3H,4Ac), 2.45(d, J=4.5 Hz, 1H, 70H), 2.35(m, 2H, H14), 2.23 (s, 3H, 10Ac),1.95 (m, 1H, H6β), 1.88(br s, 3H, Me18), 1.79(s, 1H, 1OH), (1.67,s, 3H,Me19), 1.32-1.23(m, 18H, cyclopentyl, butoxy), 1.21(s, 3H, Me17),1.12(s, 3H, Me16).

EXAMPLE 92 ##STR115## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-ethoxycarbonyl taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution of cis-1-(ethoxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one (254 mg, 0.715 mmol) in 1 mL of THF was added dropwise tothe mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 151mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-ethoxycarbonyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 151 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 118 mg of material which was purified by flashchromatography to give 100.6 mg (85%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-ethoxycarbonyl taxol, which wasrecrystallized from methanol/water.

m.p. 157-160° C.; [α]²⁵ _(Na) -62.6° (c 0.0027, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.14(d, J=7.15 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.28 (s, 1H,H10), 6.27(m, 1H, H13), 5.67(d, J=7.14 Hz, 1H, H2β), 4.96 (dd, J=8.8,1.1 Hz, 1H, H5), 4.81(d,J=9.89 Hz, 1H, NH), 4.50(b s, 1H, H2,), 4.42(dd,J=10.99, 6.59 Hz, 1H, H7), 4.30(d, J=8.24 Hz, 1H, H20α), 4.19 (d, J=8.79Hz, 1H, H20β),3.93(q, J=7.14 Hz, 2H, CH₂, ethyl), 3.79(d, J=6.59 Hz, 1H,H3),3.76(m, 1H, H3'), 3.36(m, 1H, 2'OH), 2.55(m, 1H, H6α), 2.43(s, 3H,4Ac), 2.34(m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.87 (s, 3H, Me18), 1.83(m,1H, H6β),1.73-1.64(m, 6H, cyclohexyl), 1.67 (s, 3H, Me19), 1.33-1.17(m,5H, cyclohexyl), 1.26(s, 3H, Me17), 1.14(s, 3H, Me16), 1.09 (t, J=7.14Hz, 3H, Me, ethyl).

EXAMPLE 93 ##STR116## Preparation of3'-desphenyl-3'-(cyclohexyl)-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(cyclohexyl)-azetidin-2-one(274 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(cyclohexyl)-N-debenzoyl-N-(t-butoxycarbonyl)taxoland a small amount of the (2'S,3'R) isomer.

To a solution of 155 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 106 mg (86.6%) of3'-desphenyl-3'-(cyclohexyl)-N-debenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 163-166° C.; [α]²⁵ _(Na) -71.0° (c 0.00255, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12(d, J=7.14 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.5(m, 2H, benzoate meta), 6.29 (s, 1H,H10), 6.20(bt, J=8.8 Hz, 1H, H13), 5.67(d, J=7.14 Hz, 1H, H2β), 4.96(dd, J=9.61, 2.2 Hz, 1H, H5), 4.67(d,J=9.89 Hz, 1H, NH), 4.47(dd,J=4.94, 1.65 Hz, 1H, H2'), 4.41(m, 1H, H7), 4.31(d, J=8.24 Hz, 1H,H20α), 4.17 (d, J=8.24 Hz, 1H, H20β), 3.79(d, J=7.14 Hz, 1H, H3),3.71(m,1H, H3'), 3.25(d, J=4.95 Hz, 1H, 2'OH), 2.55(m, 1H, H6α),2.47(m, 1H,70H), 2.41(s, 3H, 4Ac), 2.32(m, 2H, H14), 2.23 (s, 3H, 10Ac), 1.87 (s,3H, Me18), 1.83(m, 1H, H6β),1.73-1.58(m, 6H, cyclohexyl), 1.67 (s, 3H,Me19), 1.37-1.2(m, 5H, cyclohexyl), 1.28(s, 9H, tert-butyl), 1.25(s, 3H,Me17), 1.14(s, 3H, Me16).

EXAMPLE 94 ##STR117## Preparation of3'-desphenyl-3'-cyclohexyl-N-desbenzoyl-N-(n-butoxycarbonyl) taxol

To a solution of 7-O-triethylsilyl baccatin III (100 mg, 0.143 mmol) in1 mL of THF at -45° C. was added dropwise 0.157 mL of a 10 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(n-butoxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one(274 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-desbenzoyl-N-(n-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 155 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 111 mg (90%) of3'-desphenyl-3'-cyclohexyl-N-desbenzoyl-N-(n-butoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 140-143° C.; [α]²⁵ _(Na) -62.9° (c 0.0031, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13 (d, J=7.69 Hz, 2H, benzoateortho),7.60(m, 1H, benzoate para), 7.49(m, 2H, benzoate meta), 6.27(s,1H, H10), 6.25 (m, 1H, H13), 5.66(d, J=7.14 Hz, 1H, H2β), 4.95(d, J=8.24Hz, 1H, H5), 4.87(d,J=9.89 Hz, 1H, NH), 4.50(b s, 1H, H2'), 4.41(dd,J=10.98, 6.6 Hz, 1H, H7), 4.29(d, J=8.24 Hz, 1H, H20α), 4.17 (d, J=8.25Hz, 1H, H20β), 3.87(m, 2H, n-butyl), 3.78(d, J=7.14 Hz, 1H, H3),3.76(m,1H, H3'), 3.44(bs, 1H, 2,OH), 2.55(m, 1H, H6α), 2.43(s, 3H, 4Ac),2.34(m, 2H, H14), 2.23(s, 3H, 10Ac), 1.86(s, 3H, Me18) 1.83(m, 1H, H6β),1.75(s, 1H, 1OH), 1.73-1.64(m, 6H, cyclohexyl), 1.66 (s, 3H,Me19),1.43(m, 2H, n-butyl), 1.31-1.1.13(m, 7H, cyclohexyl, n-butyl),1.26(s, 3H, Me17), 1.14(s, 3H, Me16), 0.791(t, J=7.14 Hz, 3H, n-butyl).

EXAMPLE 95 ##STR118## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(isobutoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution of cis-1-(isobutoxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one (274 mg, 0.715 mmol) in 1 mL of THF was added dropwise tothe mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 155mg of a mixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(isobutoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 155 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 110 mg (90%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(isobutoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 145-148° C.; [α]²⁵ _(Na) -54.0° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) 6 8.14 (d, J=7.14 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.50 (m, 2H, benzoate meta), 6.28 (s, 1H, H10),6.26 (m, 1H, H13), 5.66(d, J=7.14 Hz, 1H, H2β), 4.95(dd, J=9.61, 2.2 Hz,1H, H5), 4.84(d,J=9.89 Hz, 1H, NH), 4.51(d, J=1.65 Hz, 1H, H2'),4.42(dd, J=10.44, 6.59 Hz, 1H, H7), 4.30(d, J=8.24 Hz, 1H, H20α), 4.18(d, J=8.24 Hz, 1H, H20β), 3.78(d, J=7.69 Hz, 1H, H3),3.73(m, 1H,H3'),3.70(dd, J=10.44 Hz, 6.59 Hz, 1H, isobutyl), 3.60(dd, J=10.44 Hz,6.59 Hz, 1H, isobutyl), 3.35(b s, 1H, 2'OH), 2.55(m, 1H, H6α), 2.44(s,3H, 4Ac), 2.34(m, 2H, H14), 2.23(s, 3H, 10Ac), 1.86 (s, 3H, Me18),1.83(m, 1H, H6β), 1.75(m, 1H, isobutyl), 1.73-1.58(m, 6H, cyclohexyl),1.67 (s, 3H, Me19), 1.37-1.2(m, 5H, cyclohexyl), 1.25(s, 3H, Me17),1.13(s, 3H, Me16), 0.76(d, J=7.15 Hz, 3H, Me, isobutyl), 0.71(d, J=6.59Hz, 3H, Me, isobutyl).

EXAMPLE 96 ##STR119## Preparation of3'-desphenyl-3'-cyclohexyl-N-desbenzoyl-N-(isopropoxycarbonyl) taxol

To a solution of 7-O-triethylsilyl baccatin III (100 mg, 0.143 mmol) in1 mL of THF at -45° C. was added dropwise 0.157 mL of a 10 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(isopropoxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one(264 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 153 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-desbenzoyl-N-(isopropoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 153 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 109.4 mg (90.8%) of3'-desphenyl-3'-cyclohexyl-N-desbenzoyl-N-(isopropoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 150-153° C.; [α]²⁵ _(Na) -64.1° (c 0.0031, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.14(d, J=7.14 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.29(s, 1H,H10), 6.25(m, 1H, H13), 5.67(d, J=7.14 Hz, 1H, H2β), 4.96(dd, J=10.01,2.2 Hz, 1H, H5), 4.76(d,J=9.89 Hz, 1H, NH),4.69(m, 1H, isopropyl)4.49(d, J=1.65 Hz, 1H, H2'), 4.41(dd, J=10.99, 6.59 Hz, 1H, H7), 4.30(d,J=8.24 Hz, 1H, H20α), 4.18 (d, J=8.24 Hz, 1H, H20β), 3.79(d, J=6.6 Hz,1H, H3), 3.76(m, 1H, H3'), 3.32(b s, 1H, 2'OH), 2.55(m, 1H, H6α),2.43(s, 3H, 4Ac), 2.34(m, 2H, H14), 2.23 (s, 3H, 10Ac), 1.87(s, 3H,Me18), 1.83(m, 1H, H6β), 1.73-1.64(m, 6H, cyclohexyl), 1.67 (s, 3H,Me19), 1.37-1.2(m, 5H, cyclohexyl), 1.26(s, 3H, Me17), 1.14(s, 3H,Me16), 1.11(d, J=6.04 Hz, 3H, isopropyl), 1.01(d, J=6.04 Hz, 3H,isopropyl).

EXAMPLE 97 ##STR120## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(allyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(allyloxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one(262.8 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 152.8 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(allyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 152.8 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 120 mg of material which was purified by flashchromatography to give 110.7 mg (92%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(allyloxycarbonyl) taxol, whichwas recrystallized from methanol/water.

m.p. 136-138° C.; [α]²⁵ _(Na) -61.1° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=7.14 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.28(s, 1H,H10), 6.25(m, 1H, H13), 5.75(m, 1H, allyl), 5.66(d, J=7.15 Hz, 1H, H2β),5.15(m, 1H, allyl), 5.09(m, 1H, allyl), 4.95 (m, 1H, H5), 4.92 (d,J=10.24 Hz, 1H, NH), 4.51(d, J=1.64 Hz, 1H, H2'), 4.41(m, 1H, H7),4.39(m, 2H, allyl), 4.29(d, J=8.79 Hz, 1H, H20α), 4.19 (d, J=8.79 Hz,1H, H20β), 3.79(m, 1H, H3'), 3.78(m, 1H, H3), 3.25(bs, 1H, 2'OH),2.55(m, 1H, H6α), 2.42(s, 3H, 4Ac), 2.34(m, 2H, H14), 2.23 (s, 3H,10Ac), 1.86 (s, 3H, Me18), 1.83(m, 1H, H6β),1.73-1.58(m, 6H,cyclohexyl), 1.67 (s, 3H, Me19), 1.37-1.2(m, 5H, cyclohexyl), 1.24(s,3H, Me17), 1.14(s, 3H, Me16).

EXAMPLE 98 ##STR121## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-benzyloxycarbonyl taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution of cis-1-(benzyloxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one (298 mg, 0.715 mmol) in 1 mL of THF was added dropwise tothe mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 160mg of a mixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-benzyloxycarbonyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 160 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 127 mg of material which was purified by flashchromatography to give 110 mg (86%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-benzyloxycarbonyl taxol, whichwas recrystallized from methanol/water.

m.p. 149-152° C.; [α]²⁵ _(Na) -46.5° (c 0.0023, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.14(d, J=8.8 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 7.24-7.21(m, 3H,benzyl), 7.10-7.06(m, 2H, benzyl), 6.24 (s, 1H, H10), 6.21(m, 1H, H13),5.63(d, J=7.15 Hz, 1H, H2β), 5.01(d, J=12.64 Hz, 1H,benzyl),5.00(d,J=8.79 Hz, 1H, NH),4.94 (dd, J=9.61, 2.2 Hz, 1H,H5),4.87(d, J=12.64 Hz, 1H, benzyl), 4.51(b s, 1H, H2'), 4.4(dd, J=11, 7Hz, 1H, H7), 4.28(d, J=8.79 Hz, 1H, H20α), 4.20 (d, J=8.79 Hz, 1H,H20β), 3.82(m, 1H, H3') 3.74(d, J=7.15 Hz, 1H, H3), 3.37(m, 1H, 2'OH),2.53(m, 1H, H6α), 2.43(s, 3H, 4Ac), 2.31(m, 2H, H14), 2.23 (s, 3H,10Ac), 1.83(m, 1H, H6i) 1.81 (s, 3H, Me18), 1.73-1.60(m, 6H,cyclohexyl), 1.67 (s, 3H, Me19), 1.33-1.2(m, 5H, cyclohexyl), 1.24(s,3H, Me17), 1.11(s, 3H, Me16).

EXAMPLE 99 ##STR122## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(crotyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 10 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(crotyloxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one(273 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 154.8 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(crotyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 154.8 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 113 mg (92.5%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(crotyloxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 139-141° C.; [α]²⁵ _(Na) -66.8° (c 0.00265, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13(d, J=8.79 Hz, 2H, benzoateortho),7.60(m, 1H, benzoate para),7.50(m, 2H, benzoate meta), 6.28 (s,1H, H10), 6.26 (m, 1H, H13), 5.66(d, J=7.15 Hz, 1H, H2β),5.58(m, 1H,crotyl), 5.44(m, 1H, crotyl), 4.95(dd, J=9.89 Hz, 2.2 Hz, 1H, H5),4.86(d,J=9.89 Hz,1H,NH), 4.50(dd, J=4.9 Hz, 1.92 Hz, 1H, H2'), 4.42(m,1H, H7), 4.31(m, 2H, crotyl), 4.29(d, J=8.24 Hz, 1H, H20α), 4.18 (d,J=8.24 Hz, 1H, H20β), 3.79(d, J=7.69 Hz, 1H, H3),3.75(m, 1H, H3'),3.39(d, J=4.9 Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.43(s, 3H, 4Ac), 2.31(m,2H, H14), 2.23 (s, 3H, 10Ac),1.86(s, 3H, Me18), 1.83 (m, 1H, H6β),1.73-1.64(m, 6H, cyclohexyl), 1.67 (s, 3H, Me19),1.60 (d, J=6.6 Hz, 3H,crotyl), 1.33-1.17(m, 5H, cyclohexyl), 1.26(s, 3H, Me17), 1.14(s, 3H,Me16).

EXAMPLE 100 ##STR123## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-cyclohexyloxycarbonyl taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(cyclohexyloxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one(293 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 159 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-cyclohexyloxycarbonyltaxol and a small amount of the (2'S,3'R) isomer.

To a solution of 159 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 126 mg of material which was purified by flashchromatography to give 120 mg (95%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-cyclohexyloxycarbonyl taxol,which was recrystallized from methanol/water.

m.p. 164-167° C.; [α]²⁵ _(Na) -56.5° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=8.8 Hz, 2H, benzoate ortho),7.61(m, 1H, benzoate para), 7.51(m, 2H, benzoate meta), 6.28 (s, 1H,H10), 6.25(m, 1H, H13), 5.66(d, J=7.15 Hz, 1H, H2β),4.96 (dd, J=8,79,1.65 Hz, 1H, H5) 4.76(d,J=9.89 Hz, 1H, NH), 4.50(b s, 1H, H2'), 4.41(m,2 H, H7, cyclohexyl), 4.29(d, J=8.79 Hz, 1H, H20α), 4.18 (d, J=8.79 Hz,1H, H20β), 3.79(d, J=7.15 Hz, 1H, H3),3.78(m, 1H, H3'), 3.27(m, 1H,2'OH), 2.53(m, 1H, H6α), 2.44(s, 3H, 4Ac), 2.31(m, 2H, H14), 2.24 (s,3H, 10Ac),1.87 (s, 3H, Me18) 1.83(m, 1H, H6β),1.9-0.9 (m, 21H,cyclohexyl), 1.67 (s, 3H, Me19), 1.2(s, 3H, Me17), 1.14(s, 3H, Me16).

EXAMPLE 101 ##STR124## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(trimethylsilylmethoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(trimethylsilylmethoxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one(295.8 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 159.4 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(trimethylsilylmethoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 159.4 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 126.7 mg of material which was purified by flashchromatography to give 116 mg (91.5%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(trimethylsilylmethoxycarbonyl)taxol, which was recrystallized from methanol/water.

m.p. 147-149° C.; [α]²⁵ _(Na) -56.4° (c 0.0025, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.15 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.28(s, 1H,H10), 6.26(m, 1H, H13), 5.67(d, J=7.15 Hz, 1H, H2β), 4.96 (dd, J=9.61,2.2 Hz, 1H, H5), 4.80(d,J=9.89 Hz, 1H, NH), 4.51(dd, J=4.95, 1.65 Hz,1H, H2'), 4.42(m, 1H, H7), 4.30(d, J=8.24 Hz, 1H, H20α), 4.18(d, J=8.24Hz, 1H, H20β), 3.79(d, J=7.14 Hz, 1H, H3), 3.76 (m, 1H, H3'), 3.62(d,J=14.28 Hz, 1H, CH2TMS),3.53(d, J=14.28 Hz, 1H,CH2TMS), 3.41(d, J=4.95Hz, 1H, 2'OH), 2.55(m, 1H, H6α), 2.47(m, 1H, 70H), 2.44(s, 3H, 4Ac),2.32(m, 2H, H14), 2.23(s, 3H, 10Ac), 1.86(s, 3H, Me18), 1.83(m, 1H,H6β), 1.73-1.58(m, 6H, cyclohexyl), 1.67 (s, 3H, Me19), 1.37-1.2(m, 5H,cyclohexyl), 1.26(s, 3H, Me17), 1.14(s, 3H, Me16), -0.05(s, 9H,(CH3)3Si).

EXAMPLE 102 ##STR125## Preparation ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3-hydroxybenzoyl)-10-desacetyltaxol

To a solution of2-desbenzoyl-2-(3-triethylsilyloxybenzoyl)-7,10-(bis)-O-triethylsilyl-10-desacetylbaccatin III (54.1 mg, 0.060 mmol) in 0.5 mL of THF at -45° C. was addeddropwise 0.066 mL of a 1.00 M solution of LiN(SiMe₃)₂ in hexane. After0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (90mg, 0.240 mmol) in 0.5 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before0.5 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 76.7 mg of amixture containing(2'R,3'S)-2',7,10-tris(triethylsilyl)-N-debenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3-triethylsilyloxybenzoyl)-10-desacetyltaxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 76.7 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.19 mL of pyridine at 0° C. wasadded 0.52 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 13 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 49.4 mg of material which was purified byrecrystallization to give 43.4 mg (88%) ofN-desbenzoyl-N-(t-butoxycarbonyl)-2-desbenzoyl-2-(3-hydroxybenzoyl)-10-desacetyltaxol.

m.p. 153-155° C.; [α]²⁵ _(Na) - 45.0° (c 0.560, CHCl₃).

¹ H NMR (CDC₁, 300 MHz) δ 7.36 (m, 9H, aromatic), 7.10 (m, 1H, OH), 6.38(m, 1H, H13), 5.60 (d, J=9.9 Hz, NH), 5.53 (d, J=7.5 Hz, 1H, H2β), 5.37(m, 1H, H3'), 5.18 (d, J=1.2 Hz, 1H, H10), 4.90 (dd, J=9.9, 2.4 Hz, 1H,H5), 4.75 (m, 1H, H2'), 4.29 (d, J=8.4 Hz, 1H, H20α), 4.24 (m, 2H, H7,H20β), 3.93 (d, J=7.5 Hz, 1H, H3), 3.29 (m, 1H, 2'OH), 2.56 (m, 1H,H6α), 2.36 (s, 3H, 4Ac), 2.27 (m, 2H, H14), 1.91 (s, 3H, Me18), 1.85 (m,1H, H6β), 1.76 (s, 3H, Me19), 1.33 (s, 9H, t-butyl), 1.24 (s, 3H, Me17),1.08 (s, 3H, Me16).

EXAMPLE 103 ##STR126## Preparation of N-debenzoyl-N-(isobutoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (200 mg, 0.286 mmol) in 2mL of THF at -45° C. was added dropwise 0.174 mL of a 1.63M solution ofnBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(isobutoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (540mg, 1.43 mmol) in 2 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 308 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(isobutoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 308 mg (0.286 mmol) of the mixture obtained from theprevious reaction in 18 mL of acetonitrile and 0.93 mL of pyridine at 0°C. was added 2.8 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 243 mg of material which was purified by flashchromatography to give 208 mg (86%) of N-debenzoyl-N-(isobutoxycarbonyl)taxol, which was recrystallized from methanol/water.

m.p. 149-151° C.; [α]²⁵ _(Na) -61.03° (c 0.0097, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (d, J=7.7 Hz, 2H, benzoate ortho),7.64-7.30 (m, 8H, aromatic), 6.28 (s, 1H, H10), 6.24 (dd, J=8.2, 8.2 Hz,1H, H13), 5.66 (d, J=6.6 Hz, 1H,H2β), 5.57 (dd, 1H, H3'), 5.29 (d, J=8.4Hz, 1H,NH), 4.94 (d,J=8.2 Hz, 1H, H5), 4.63 (br s,1H, H2'), 4.41 (m, 1H,H7), 4.28 (d, J=8.2 Hz, 1H, H20α), 4.18 (d, J=8.7 Hz, 1H, H20β), 3.79(d, J=7.1 Hz, 1H, H3 ), 3.72 (m, 2H, isobutyl), 3.37 (d, J=4.9 Hz,1H,2'OH), 2.55 (m, 1H, H6α), 2.49 (d, J=3.8 Hz, 1H, 70H), 2.37 (s, 3H,4Ac), 2.31 (m, 2H, H14), 2.23 (s, 3H, 10Ac), 2.21 (m, 1H, isobutyl),1.87 (m, 1H, H6β), 1.82 (br s, 3H, Me18), 1.77 (s, 1H, 1OH), 1.67 (s,3H, Me19), 1.26 (s, 3H, Me17), 1.14 (s, 3H, Me16), 0.78 (t, 3H,isobutyl).

EXAMPLE 104 ##STR127## Preparation of N-debenzoyl-N-(isopropoxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(isopropoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one(260 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 152 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(isopropoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 152 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 120 mg of material which was purified by flashchromatography to give 106 mg (88%) ofN-debenzoyl-N-(isopropoxycarbonyl) taxol, which was recrystallized frommethanol/water.

m.p. 151-154° C.; [α]²⁵ _(Na) -68.8° (c 0.0043, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.64-7.30 (m, 8H, aromatic), 6.28 (s, 1H, H10), 6.25-6.22 (m, 1H, H13 ),5.66 (d, J=7.1 Hz, 1H, H2β)), 5.48 (d, J=9.3 Hz,1H,H3'), 5.28(br,1H,NH),4.93 (d, J=7.7 Hz, 1H, H5), 4.77 (m, 1H, isopropyl), 4.63 (br s,1H,H2'), 4.40 (m, 1H, H7), 4.30 (d, J=8.2 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz,1H, H20β), 3.80 (d, J=6.6 Hz, 1H, H3), 3.39 (br s, 1H, 2'OH), 2.53 (m,1H, H6α), 2.37 (s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.87(br m, 1H, H6β), 1.83 (br s, 3H, Me18), 1.68 (s, 3H, Me19), 1.26 (s, 3H,Me17), 1.14 (s, 3H, Me16), 1.08 (d, J=6 Hz, 6H,isopropyl).

EXAMPLE 105 ##STR128## Preparation of N-debenzoyl-N-(allyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1rnL of THF at -45° C. was added dropwise 0.087 mL of a 1.63 M solutionof n-BuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(allyloxycarbonyl)-3-triethylsilyloxy-4-phenyl azetidin-2-one (258mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 152 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(allyloxycarbonyl) taxoland a small amount of the (2'S,3'R) isomer.

To a solution of 152 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 120 mg of material which was purified by flashchromatography to give 106 mg (88%) of N-debenzoyl-N-(allyloxycarbonyl)taxol, which was recrystallized from methanol/water.

m.p. 145-147° C.; [α]²⁵ _(Na) -66.8° (c 0.005, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.20 (m, 8H, aromatic), 6.28 (s, 1H, H10), 6.25 (m, 1H, H13 ), 5.80(m, 1H, allylic), 5.66 (d, 2H, H2b & H3'), 5.30 (d, J=9.3 Hz,1H,NH),5.16 (br m,2H,allylic), 4.93 (dd, 1H, H5), 4.65 (br s,1H, H2'),4.51-4.37 (m, 3H, H7 & allylic), 4.29 (d, J=8.2 Hz, 1H, H20α), 4.17 (d,J=8.2 Hz, 1H, H20β), 3.79 (d, J=6.6 Hz, 1H, H3), 3.39 (br s, 1H, 2'OH),2.55 (m, 1H, H6α), 2.36 (s, 3H, 4Ac), 2.24 (s, 3H, 10Ac), 1.87 (br m,1H, H6β), 1.82 (br s, 3H, Me18), 1.67 (s, 3H, Me19), 1.26 (s, 3H, Me17),1.14 (s, 3H, Me16).

EXAMPLE 106 ##STR129## Preparation of N-debenzoyl-N-(benzyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(benzyloxycarbonyl)-3-(2-methoxy-2-propoxy)-4-phenylazetidin-2-one (264 mg, 0.715 mmol) in 1 mL of THF was added dropwise tothe mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 153mg of a mixture containing(2'R,3'S)-2'-(O-2-methoxy-2-propyl),7-triethylsilyl-N-debenzoyl-N-(benzoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 153 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 126 mg of material which was purified by flashchromatography to give 106 mg (84%) of N-debenzoyl-N-(benzoxy-carbonyl)taxol, which was recrystallized from methanol/water.

m.p. 144-146° C.; [α]²⁵ _(Na) -54.28° (c 0.00245, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12 (d, J=7.1 Hz, 2H, benzoate ortho),7.64-7.16 (m, 13H, aromatic), 6.26-6.20 (br m, 2H, H10 & H13), 6.25-6.22(m, 1H, H13 ),5.66 (m, 2H, H3' & H2β)), 5.34 (d, J=9.7 Hz,1H,NH),5.08-4.95 (dd, 2H, benzylic),4.94 (d,1H, H5), 4.66 (br s,1H, H2'), 4.40(m, 1H, H7), 4.23 (d, J=8.8 Hz, 1H, H20c), 4.18 (d, J=8.2 Hz, 1H, H20β),3.76 (d, J=7.1 Hz, 1H, H3), 3.34 (br s, 1H, 2'OH), 2.54 (m, 1H, H6α),2.36 (s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.23 (s, 3H, 10Ac), 1.87 (m, 1H,H6β), 1.82 (br s, 3H, Me18), 1.67 (s, 3H, Me19), 1.23 (s, 3H, Me17),1.14 (s, 3H, Me16).

EXAMPLE 107 ##STR130## Preparation ofN-debenzoyl-N-(3-butynyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(3-butynyloxycarbonyl)-3-triethylsilyloxy-4-(2-phenyl)azetidin-2-one(267 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 154 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(3-butynyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 154 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 121 mg of material which was purified by flashchromatography to give 106 mg (87%) of N-debenzoyl-N-(3-butynyloxycarbonyl) taxol, which was recrystallized from methanol/water.

m.p. 147-149° C.; [α]²⁵ _(Na) -58.5° (c 0.005, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.30 (m, 8H, aromatic), 6.30-6.24 (br m, 2H,H10 & H13),5.66 (d, 2H,H2b&H3'), 5.30(d,J=9.3 Hz,1H,NH), 4.93 (dd, 1H, H5), 4.64 (br s,1H,H2'), 4.40 (m, 1H, H7), 4.29 (d, J=8.8 Hz, 1H, H20α), 4.18 (d, J=8.8Hz, 1H, H20β), 4.06 (t, 2H, butynoxy), 3.80 (d, J=7.1 Hz, 1H, H3), 3.37(br s, 1H, 2'OH), 2.53 (m, 1H, H6α), 2.40 (t, 2H, H14), 2.36 (s, 3H,4Ac), 2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.94 (br m, 1H, butynoxy),1.87 (m, 1H, H6β), 1.83 (br s, 3H, Me18), 1.68 (s, 3H, Me19), 1.26 (s,3H, Me17), 1.14 (s, 3H, Me16).

EXAMPLE 108 ##STR131## Preparation of N-debenzoyl-N-(crotyloxycarbonyl)taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(crotyloxycarbonyl)-3-triethylsilyloxy-4-phenyl azetidin-2-one(268 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0 ,C and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NAHCO, and 60/40 ethyl acetate/hexane. Evaporation of the organic layer gave a residue which waspurified by filtration through silica gel to give 154 mg of a mixturecontaining(2'R,3'S)-2',7-(bis)-triethylsilyl-N-debenzoyl-N-(crotyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 154 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aq ueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solu tion gave 121 mg of m aterial which was purified by flashchromatography to give 108 mg (89%) of N-debenzoyl-N-(crotyloxycarbonyl)taxol, which was recrystallized from methanol/water.

m.p. 132-135° C.; [α]²⁵ _(Na) -49.8° (c 0.00235, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.1 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.30 (m, 8H, aromatic), 6.28 -6.22 (m, 2H, H13 & H10) ),5.67-5.44(m, 4H, H3'crotyl & H2β)), 5.30(d, J=7.7, 1H,NH), 4.94 (d, J=8.2 Hz, 1H,H5), 4.63 (br s,1H, H2'), 4.25 (m, 3H, H7 & crotyl CH₂), 4.28 (d, J=8.8Hz, 1H, H20α), 4.18 (d, J=8.8 Hz, 1H, H20β), 3.79 (d, J=7.1 Hz, 1H, H3),3.37 (br, 1H, 2'OH), 2.55 (m, 1H, H6α), 2.36 (s, 3H, 4Ac), 2.31 (m, 2H,H14), 2.23 (s, 3H, 10Ac), 1.88 (m, 1H, H6β), 1.82 (br s, 3H, Me18), 1.67(s, 3H, Me19), 1.64 (d, 3H, crotyl methyl), 1.26 (s, 3H, Me17), 1.14 (s,3H, Me16).

EXAMPLE 109 ##STR132## Preparation ofN-debenzoyl-N-(cyclohexyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(cyclohexyloxycarbonyl)-3-triethylsilyloxy-4-(2-phenyl)azetidin-2-one(288 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 158 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-N-debenzoyl-N-(cyclohexyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 158 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 125 mg of material which was purified by flashchromatography to give 112 mg (90%) ofN-debenzoyl-N-(cyclohexyloxycarbonyl) taxol, which was recrystallizedfrom methanol/water.

m.p. 159-161° C.; [α]²⁵ _(Na) -59.26° (c 0.0054, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13 (d, J=7.1 Hz, 2H, benzoate ortho),7.64-7.30 (m, 8H, aromatic), 6.26 (br s, 2H, H10 & H13), 5.65 (d, J=7.1Hz, 1H, H2β)), 5.51 (d, J=9.3 Hz,1H,H3'), 5.31(br,1H,NH), 4.93 (dd,1H,H5), 4.65 (br s,1H, H2'), 4.53-4.38 (m, 2H, H7 & cyclohexyl), 4.32 (d,J=8.2 Hz, 1H, H20α), 4.16 (d, J=8.2 Hz, 1H, H20β), 3.80 (d, J=7.1 Hz,1H, H3), 3.37 (br s, 1H, 2,OH), 2.53 (m, 1H, H6α), 2.38 (s, 3H, 4Ac),2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.87 (br m, 1H, H6β), 1.83 (br s,3H, Me18), 1.67 (s, 3H, Me19), 1.26 (s, 3H, Me17), 1.14 (s, 3H, Me16).

EXAMPLE 110 ##STR133## Preparation ofN-debenzoyl-N-(1,3-diethoxy-2-propyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(1,3-diethoxy-2-propyloxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (323 mg, 0.715 mmol) in 1 mL of THF was added dropwise tothe mixture.

The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 165 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(1,3-diethoxy-2-propyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 165 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 132 mg of material which was purified by flashchromatography to give 106 mg (88%) ofN-debenzoyl-N-(1,3-diethoxy-2-propyloxycarbonyl) taxol, which wasrecrystallized from methanol/water.

m.p. 119-122° C.; [α]²⁵ _(Na) -58.9° (c 0.0056, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.14 (d, J=7.1 Hz, 2H, benzoate ortho),7.64-7.30 (m, 8H, aromatic), 6.34 (m, 1H, H13), 6.28 (s, 1H, H10 ),5.68(d, 2H, H2b&H3'), 5.34(d,1H,NH), 4.96 (dd, 1H, H5), 4.80 (m, 1H, 1,3diethoxy 2-propyl), 4.65 (br s,1H, H2'), 4.41 (m, 1H, H7), 4.29 (d,J=8.2 Hz, 1H, H20α), 4.19 (d, J=8.2 Hz, 1H, H20β), 3.80 (d, J=7.1 Hz,1H, H3), 3.42 (m, 9H, 1,3 diethoxy 2-propyl & 2'OH), 2.53 (m, 1H, H6α),2.40 (s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.87 (br m,1H, H6β), 1.84 (br s, 3H, Me18), 1.68 (s, 3H, Me19), 1.25 (s, 3H, Me17),1.14 (s, 3H, Me16), 1.08 (m,6H,1,3 diethoxy 2-propyl).

EXAMPLE 111 ##STR134## Preparation ofN-debenzoyl-N-(2-methoxyethoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(2-methoxyethoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one (271 mg, 0.715 irrol) in 1 mL of THF was added dropwiseto the mixture. The solution was warmed to 0° C. and kept at thattemperature for 1 h before 1 mL of a 10% solution of AcOH in THF wasadded. The mixture was partitioned between saturated aqueous NaHCO₃ and60/40 ethyl acetate/hexane. Evaporation of the organic layer gave aresidue which was purified by filtration through silica gel to give 154mg of a mixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-N-debenzoyl-N-(2-methoxyethoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 154 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 107 mg (87%) ofN-debenzoyl-N-(2-methoxyethoxycarbonyl) taxol, which was recrystallizedfrom methanol/water.

m.p. 143-146° C.; [α]²⁵ _(Na) -40.94° (c 0.0043, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12 (d, J=7.1 Hz, 2H, benzoate ortho),7.62-7.30 (m, 8H, aromatic), 6.27 (br m, 2H, H10 & H13), 5.67 (d, 2H,H2p & H3'), 5.31(d, J=9.3 Hz, 1H,NH), 4.93 (dd, 1H, H5), 4.64 (br s,1H,H2'), 4.40 (m, 1H, H7), 4.30 (d, J=8.2 Hz, 1H, H20α), 4.18 (d, J=8.8 Hz,1H, H20β), 4.17-3.98 (m, 2H, 2-methoxyethyl), 3.79 (d, J=7.1 Hz, 1H,H3), 3.42-3.32 (m, 2H, methoxyethyl), 3.29 (s, 3H, OMe), 2.55 (m, 1H,H6α), 2.38 (s, 3H, 4Ac), 2.33 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.88 (m,1H, H6β), 1.82 (br s, 3H, Me18), 1.67 (s, 3H, Me19), 1.26 (s, 3H, Me17),1.14 (s, 3H, Me16).

EXAMPLE 112 ##STR135## Preparation ofN-debenzoyl-N-(neopentyloxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1 M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(neopentyloxycarbonyl)-3-triethylsilyloxy-4-(2-phenyl)azetidin-2-one(280 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 156 mg of amixture containing(2'R,3'S)-2',7-(bis)-triethylsilyl-N-debenzoyl-N-(neopentyloxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 156 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 124 mg of material which was purified by flashchromatography to give 106 mg (86%) ofN-debenzoyl-N-(neopentyloxycarbonyl) taxol, which was recrystallizedfrom methanol/water.

m.p. 160-162° C.; [α]²⁵ _(Na) -61.0° (c 0.00515, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.13 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.26 (m, 8H, aromatic), 6.27-6.22 (br s, 2H, H10 & H13), 5.66 (d,J=7.1 Hz, 1H, H2β)), 5.56 (br m, 1H,H3'), 5.30 (br,1H,NH), 4.94 (d,J=7.7 Hz, 1H, H5), 4.66 (br s,1H, H2'), 4.40 (m, 1H, H7), 4.29 (d, J=8.2Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β), 3.80 (d, J=6.6 Hz, 1H, H3),3.72-3.58 (m, 2H, neopentyl), 3.38 (br s, 1H, 2'OH), 2.52 (m, 1H, H6α),2.38 (br s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.87 (br m,1H, H6β), 1.83 (br s, 3H, Me18), 1.67 (s, 3H, Me19), 1.25 (s, 3H, Me17),1.14 (s, 3H, Me16), 0.80 (s, 9H, neopentyl).

EXAMPLE 113 ##STR136## Preparation of3'-desphenyl-3'-(3-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-O-triethylsilyl baccatin III (100 mg, 0.143 mmol) in1 mL of THF at -45° C. was added dropwise 0.157 mL of a 1M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution of cis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(3-furyl)azetidin-2-one (262 mg,0.715 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 153 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-(3-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 153 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 120 mg of material which was purified by flashchromatography to give 112 mg (93%) of3'-desphenyl-3'-(3-furyl)-N-desbenzoyl-N-(t-butoxycarbonyl) taxol, whichwas recrystallized from methanol/water.

m.p. 154-156° C.; [α]²⁵ _(Na) -72° (c 0.0065 , CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.12 (d, J=7.1 Hz, 2H, benzoate ortho),7.64-7.43 (m, 5H, aromatic), 6.45 (s, 1H, 3-furyl), 6.30 (s, 1H, H10),6.23(m, 1H, H13), 5.67 (d, J=7.1 Hz,1H, H2β)), 5.19 (d,1H,H3'), 5.09(d,J=9.8 Hz, 1H,NH), 4.94 (d,J=9.3 Hz, 1H, H5), 4.53 (dd,1H, H2'), 4.41(m, 1H, H7), 4.31 (d, J=8.2 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β),3.81 (d, J=7.1 Hz, 1H, H3), 3.37 (d, J=5.5 Hz, 1H, 2'OH), 2.53 (m, 1H,H6α), 2.47 (d,1H, 7 OH), 2.34 (s, 3H, 4Ac), 2.24 (s, 3H, 10Ac),1.92-1.83 (m, 1H, H6β), 1.87 (br s, 3H, Me18), 1.67 (s, 3H, Me19), 1.33(s, 9H, t-butyl), 1.25 (s, 3H, Me17), 1.15 (s, 3H, Me16).

EXAMPLE 114 ##STR137## Preparation of3'-desphenyl-3'-(3-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-O-triethylsilyl baccatin III (100 mg, 0.143 mmol) in1 mL of THF at -45° C. was added dropwise 0.157 mL of a 1M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution of cis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(3-thienyl)azetidin-2-one (274mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h before1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 155 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-(3-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 155 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 111 mg (93%) of3'-desphenyl-3'-(3-thienyl)-N-desbenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 155-157° C.; [α]²⁵ _(Na) -63.8° (c 0.0097 , CHCl₃).

¹ H NMR (CD_(C1), 300 MHz) 8 8.11 (d, J=7.1 Hz, 2H, benzoate ortho),7.63-7.30 (m, 5H, aromatic), 7.11 (dd, 1H, 3-thienyl), 6.30 (s, 1H,H10), 6.23(m, 1H, H13), 5.67 (d, J 7.1 Hz,1H, H2β)), 5.32 (d,1H,H3'),5.23 (d,J=9.9 Hz, 1H,NH), 4.94 (dd, 1H, H5), 4.62 (dd,1H, H2'), 4.41 (m,1H, H7), 4.30 (d, J=8.2 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β),3.78 (d, J=6.6 Hz, 1H, H3), 3.38 (d, J=5.5 Hz, 1H, 2'OH), 2.53 (m, 1H,H6α), 2.47 (d, J=4.4 Hz,1H, 7 OH), 2.34 (s, 3H, 4Ac), 2.24 (s, 3H,10Ac), 1.87 (br s, 3H, Me18), 1.67 (s, 3H, Me19), 1.33 (s, 9H, t-butyl),1.25 (s, 3H, Me17), 1.15 (s, 3H, Me16).

EXAMPLE 115 ##STR138## Preparation of3'-desphenyl-3'-(4-pyridyl)-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(4-pyridyl)azetidin-2-one(270 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 154 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-(4-pyridyl)-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 154 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 115 mg (94%) of3'-desphenyl-3'-(4-pyridyl)-N-debenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from methylene chloride/hexane.

m.p. 134-136° C.; [α]²⁵ _(Na) -65.8° (c 0.00205 , CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.64 (br,2H, 2-pyridyl), 8.10 (d, J=7.1 Hz,2H, benzoate ortho), 7.63-7.31 (m, 5H, aromatic), 6.27 (br, 2H, H10 &H13), 5.66 (d, J=7.1 Hz,1H, H2β)), 5.45 (d,1H,H3'), 5.30 (d, J=9.3 Hz,1H,NH), 4.94 (dd,1H, H5), 4.68 (br s,1H, H2'), 4.40 (m, 1H, H7), 4.30(d, J=8.2 Hz, 1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β), 3.80 (d, J=7.1Hz, 1H, H3), 3.60 (br, 1H, 2'OH), 2.53 (m, 1H, H6α), 2.37 (s, 3H, 4Ac),2.31 (m, 2H, H14), 2.24 (s, 3H, 10Ac), 1.85 (br s, 3H, Me18), 1.67 (s,3H, Me19), 1.32 (br s, 9H, t-butyl), 1.24 (s, 3H, Me17), 1.15 (s, 3H,Me16).

EXAMPLE 116 ##STR139## Preparation of3'-desphenyl-3'-(2-pyridyl)-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(2-pyridyl)azetidin-2-one(270 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 154 mg of amixture containing(2'R,3'S)-2',7-(bis)tri-ethylsilyl-3'-desphenyl-3'-(2-pyridyl)-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 154 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 TL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 105 mg (86%) of3'-desphenyl-3'-(2-pyridyl)-N-debenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from methylene chloride/hexane.

m.p. 144-147° C.; [α]²⁵ _(Na) -72.4° (c 0.0025 , CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.50 (d, J=4.9 Hz, 1H, 2-pyridyl), 8.12 (d,J=7.1 Hz, 2H, benzoate ortho), 7.76(m, 1H, 2-pyridyl), 7.63-7.23 (m, 5H,aromatic), 6.29 (s, 1H, H10), 6.18(m, 1H, H13), 5.83 (d, 1H, H2β)), 5.66(d, 1H, H3'), 5.36 (d, J=10.4 Hz, 1H,NH), 5.10 (d, 1H, 70H), 4.97(dd,1H, H5), 4.79 (br,1H, H2'), 4.44 (m, 1H, H7), 4.30 (d, J=8.2 Hz, 1H,H20α), 4.16 (d, J=8.2 Hz, 1H, H20β), 3.82 (d, J=6.6 Hz, 1H, H3), 2.53(m, 1H, H6α), 2.45 (s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.23 (s, 3H, 10Ac),1.90-1.85 (m, 1H, H6β), 1.83 (br s, 3H, Me18), 1.67 (s, 3H, Me19), 1.42(br s, 9H, t-butyl), 1.22 (s, 3H, Me17), 1.13 (s, 3H, Me16).

EXAMPLE 117 ##STR140## Preparation of3'-desphenyl-3'-(3-pyridyl)-N-desbenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-O-triethylsilyl baccatin III (100 mg, 0.143 mmol) in1 mL of THF at -45° C. was added dropwise 0.157 mL of a 1M solution ofLHMDS in THF. After 0.5 h at -45° C., a solution of cis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(3-pyridyl)azetidin-2-one (270mg, 0.715 nmmol) in 1 mL of THF was added dropwise to the mixture. Thesolution was warmed to 0° C. and kept at that temperature for 1 h beforeI mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 154 mg of amixture containing(2'R,3'S)-2',7-(bis)-O-triethylsilyl-3'-desphenyl-3'-(3-pyridyl)-N-desbenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 154 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 122 mg of material which was purified by flashchromatography to give 115 mg (94%) of3'-desphenyl-3'-(3-pyridyl)-N-desbenzoyl-N-(t-butoxycarbonyl) taxol,which was recrystallized from methylene chloride/hexane.

m.p. 139-142° C.; [α]²⁵ _(Na) -69.1° (c 0.00205 , CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.61 (br,2H, 3-pyridyl), 8.12 (d, J=7.1 Hz,2H, benzoate ortho), 7.77 (d, 1H, 3-pyridyl), 7.64-7.47 (m, 3H, aromaticbenzoate), 7.33 (m, 1H, 3-pyridyl), 6.29 (s, 1H, H10), 6.28-6.24 (m, 1H,H13), 5.67 (d, J=7.1 Hz,1H, H2β)), 5.43 (d,1H,H3'), 5.29 (d,1H,NH), 4.96(dd,1H, H5), 4.62 (br s,1H, H2'), 4.44 (m, 1H, H7), 4.31 (d, J=8.2 Hz,1H, H20α), 4.17 (d, J=8.2 Hz, 1H, H20β), 3.80 (d, J=7.1 Hz, 1H, H3),3.58 (br, 1H, 2'OH), 2.53 (m, 1H, H6α), 2.40 (s, 3H, 4Ac), 2.31 (m, 2H,H14), 2.24 (s, 3H, 10Ac), 1.90-1.85 (m, 1H, H6β), 1.83 (br s, 3H, Me18),1.67 (s, 3H, Me19), 1.35 (br s, 9H, t-butyl), 1.25 (s, 3H, Me17), 1.15(s, 3H, Me16).

EXAMPLE 118 ##STR141## Preparation of3'-desphenyl-3'-hydroxymethyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.00 M solution oflithium bis(trimethylsilyl)amide in THF. After 0.5 h at -45° C., asolution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-triethylsilyloxymethylazetidin-2-one(316 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 163.5 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-hydroxymethyl-N-debenzoyl-N-(t-butoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 163.5 mg of the mixture obtained from the previousreaction in 4 mL of acetonitrile and 0.3 mL of pyridine at 0° C. wasadded 1.2 mL of 48% aqueous HF. The mixture was stirred at 0° C. for 3h, then at 25° C. for 24 h, and partitioned between saturated aqueoussodium bicarbonate and ethyl acetate. Evaporation of the ethyl acetatesolution gave 114.9 mg of material which was purified by plug filtrationand recrystallization from methanol/water to give 109.0 mg (95%) of3'-desphenyl-3'-hydroxymethyl-N-debenzoyl-N-(t-butoxycarbonyl) taxol.

m.p. 162-163° C.; [α]²⁵ _(Na) -60 (c 0.001, CHCl₃).

¹ H NMR (CDCl₃, 500 MHz) δ 8.10(d, J=7.3 Hz, 2H, benzoate ortho),7.70-7.40(m, 3H, aromatic), 6.31(s, 1H, H10), 6.20 (dd, J=9.3, 9.3 Hz,1H, H13), 5.67(d, J=6.8, 1H , H2β), 4.96(m, 2H, H5+NH),4.57(dd, J=5.4,2.2 Hz,1H, H2'), 4.42 (m, 1H, H7), 4.37(d, J=8.2 Hz, 1H, H20α), 4.18(br, 2H, H3'+H20β), 3.82 (m,2H, H3+CH2OH), 3.35(d, J=2.2 Hz.1H,H2'),2.56(m, 1H, H6α), 2.47(m, 1H, 70H), 2.39 (s, 3H, 4Ac), 2.34(m, 2H,H14s), 2.24(s, 3H, 10Ac), 2,18(brs, 1H,CH2OH), 1.90(br s, 3H, Me18),1.83(m, 1H, H6β), 1.71 (s, 1H, 1OH), 1.67(s, 3H, Me19), 1.24 (s, 3H,Me17), 1.22(s, 9H, t-butyl), 1.14(s, 3H, Me16).

EXAMPLE 119 ##STR142## Preparation of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(neopentoxycarbonyl) taxol

To a solution of 7-triethylsilyl baccatin III (100 mg, 0.143 mmol) in 1mL of THF at -45° C. was added dropwise 0.157 mL of a 1.0 M solution oflithium bis(trimethylsilyl)amide in THF. After 1 h at -45° C., asolution ofcis-1-(neopentoxycarbonyl)-3-triethylsilyloxy-4-cyclohexylazetidin-2-one(284.3 mg, 0.715 mmol) in 1 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 157 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(neopentoxycarbonyl)taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 157 mg (0.143 mmol) of the mixture obtained from theprevious reaction in 6 mL of acetonitrile and 0.3 mL of pyridine at 0°C. was added 0.9 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 124.4 mg of material which was purified by flashchromatography to give 106 mg (85.2%) of3'-desphenyl-3'-cyclohexyl-N-debenzoyl-N-(neopentoxycarbonyl) taxol,which was recrystallized from methanol/water.

m.p. 159-161° C.; [α]²⁵ _(Na) -60.0° (c 0.0026, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.15(d, J=7.14 Hz, 2H, benzoate ortho),7.60(m, 1H, benzoate para), 7.50(m, 2H, benzoate meta), 6.28(s, 1H,H10), 6.25(m, 1H, H13), 5.66(d, J=7.15 Hz, 1H, H2β), 4.95(dd, J=9.61,1.65 Hz, 1H, H5), 4.86(d,J=9.89 Hz, 1H, NH), 4.52(d, J=1.65 Hz, 1H,H2'), 4.42(dd, J=10.99 Hz, 6.6 Hz, 1H, H7), 4.30(d, J=8.24 Hz, 1H,H20α), 4.18(d, J=8.24 Hz, 1H, H20β), 3.79(d, J=7.15 Hz, 1H, H3), 3.78(m,1H, H3'), 3.65(d, J=10.44 Hz, 1H, neopentyl),3.52(d, J=10.44 Hz, 1H,neopentyl), 3.25(bs, 1H, 2'OH), 2.55(m, 1H, H6α), 2.44(s,3H, 4Ac),2.32(m, 2H, H14), 2.23 (s, 3H, 10Ac), 1.86 (s, 3H, Me18), 1.83(m, 1H,H6β), 1.73-1.58 (m, 6H, cyclohexyl), 1.67 (s, 3H, Me19), 1.37-1.2(m, 5H,cyclohexyl), 1.25(s, 3H, Me17), 1.13(s, 3H, Me16), 0.76(s, 9H,neopentyl).

EXAMPLE 120 ##STR143## Preparation ofN-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-(4-nitrophenyl) taxol

To a solution of 7-triethylsilyl baccatin III (120 mg, 0.171 mmol) in1.2 mL of THF at -45° C. was added dropwise 0.104 mL of a 1.63M solutionof nBuLi in hexane. After 0.5 h at -45° C., a solution ofcis-1-(t-butoxycarbonyl)-3-triethylsilyloxy-4-(4-nitrophenyl)azetidin-2-one(361 mg, 0.885 mmol) in 1.2 mL of THF was added dropwise to themtixture. The solution was warmed to 0° C. and kept at that temperaturefor 1 h before 1 mL of a 10% solution of AcOH in THF was added. Themixture was partitioned between saturated aqueous NaRCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 192 mg of amixture containing(2'R,3'S)-2',7-(bis)triethylsilyl-N-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-(4-nitrophenyl)taxol and a very small amount of the (2'S,3'R) isomer.

To a solution of 192 mg (0.171 mmol) of the mixture obtained from theprevious reaction in 11 mL of acetonitrile and 0.55 mL of pyridine at 0°C. was added 1.7 mL of 48% aqueous HF. The mixture was stirred at 0° C.for 3 h, then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 153 mg of material which was purified by flashchromatography to give 140.0 mg (91t) ofN-debenzoyl-N-(t-butoxycarbonyl)-3'-desphenyl-3'-(4-nitrophenyl) taxol,which was recrystallized from methanol/water.

m.p. 172-173° C; [α]²⁵ _(Na) -54.0° (c 0.0046, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.25 (d, J=8.7 Hz, 2H, Ar--NO₂), 8.10 (d,J=7.2 Hz, 2H, benzoate ortho), 7.6-7.46 (m, 5H, aromatic), 6.29 (s, 1H,H10), 6.29 (dd, J=8.3, 8.3 Hz, 1H, H13), 5.66 d, J=6.6 Hz, 1H, H20α),5.46 (m, 2H, H3', NH), 4.94 (d, J=9.3 Hz, 1H, H5), 4.67 (br s, 1H, H2'),4.40 (m, 1H, H7), 4.31 (d, J=8.2 Hz, 1H, H20α), 4.16(d, J=8.2 Hz, 1H,H20β), 3.80(d, J=7.1 Hz, 1H, H3), 3.52 (br s, 1H, 2'OH), 2.54 (m, 1H,H6α), 2.45 (m, 1H, 70H), 2.38 (s, 3H, 4Ac), 2.31 (m, 2H, H14), 2.24 (s,3H, 10Ac), 1.89 (m, 1H, H6), 1.85 (br s, 3H, Me18), 1.72 (s, 1H, 1OH),1.67 (s, 3H, Me19), 1.31(s, 9H, t-butyl), 1.26 (S, 3H, Me17), 1.15(s,3H, Me16).

EXAMPLE 121 ##STR144## Preparation ofN-debenzoy-N-(ethoxycarbonyl)-3'-desphenyl-3'-(4-nitrophenyl) taxol

To a solution of 7-triethylsilyl baccatin III (120 mg, 0.171 mmol) in1.2 mL of THF at -45° C. was added dropwise 0.104 mL of a 1.63M solutionof nBuLi in hexane. After 0.5 h at -45° C. a solution ofcis-1-(ethoxycarbonyl)-3-triethylsilyloxy-4-(4-nitrophenyl)azetidin-2-one(337 mgt 0.885 mmol) in 1.2 mL of THF was added dropwise to the mixture.The solution was warmed to 0° C. and kept at that temperature for 1 hbefore 1 mL of a 10% solution of AcOH in THF was added. The mixture waspartitioned between saturated aqueous NaHCO₃ and 60/40 ethylacetate/hexane. Evaporation of the organic layer gave a residue whichwas purified by filtration through silica gel to give 187 mg of amixture containing(2'R,3'S)-2',7-(bisitriethylsilyl-N-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-(4-nitropbenyl) taxol and a small amount of the (2'S,3'R) isomer.

To a solution of 187 mg (0.171 mmol) of the mixture obtained from theprevious reaction in 11 mL of acetonitrile and 0.55 mnL of pyridine at0° C. was added 1.7 mL of 48% aqueous HF. The mixture was stirred at 0°C. for 3 h. then at 25° C. for 13 h, and partitioned between saturatedaqueous sodium bicarbonate and ethyl acetate. Evaporation of the ethylacetate solution gave 148 mg of material which was purified by flashchronatography to give 134.0 mg (90%) ofN-debenzoyl-N-(ethoxycarbonyl)-3'-desphenyl-3'-(4-nitrophenyl) taxol,which was recrystallized from methanol/water.

m.p.172-173° C.; [α]²⁵ _(Na) -58.0° (C 0.0051, CHCl₃).

¹ H NMR (CDCl₃, 300 MHz) δ 8.26(d, J=8.7 jiz, 2H, Ar--NO₂), 8.10 (d,J=7.2 Hz, 2H, benzoate ortho), 7.6-7.46 (m, 5H, aromatic), 6.32(br t,1H, H13), 6.29 (s, 1H, H10) 5.i65 (m, 2H, H3',H2β), 5.45 (br d, 1H, NH),4.93 (d, J=9.3 Hz, 1H, H5) 4. 68 (br s, 1H, H2'), 4.39 (m, 1H, H7), 4.30(d, J=8.8 Hz, 1H, H20α), 4.17(d, J=8.8 Hz, 1H, H20β), 4.01(dd,J=13.7,6.6 Hz, 2H, OCH2), 3.80(d, J=6.6 Hz, 1H, H3), 3.61 (d, J=3.8 Hz,1H, 2'OH), 2.55 (m, 1H, H6α), 2.46 (d, J=3.9 Hz, 1H, 70H),2.38 (s, 3H,4Ac), 2.28 (m, 2H, H14), 2.16 (s, 3H, 10Ac), 1.91 (m, 1H, H6β), 1.84 (brs, 3H, Me18), 1.74 (s, 1H, 10H), 1.68 (s, 3H, Me19), 1.26(s, 3H, Me17),1.13(m, 6H, Me16, Et).

EXAMPLE 122

The taxanes of the preceding examples were evaluated in in vitrocytotoxicity activity against human colon carcinoma cells HCT-116.Cytotoxicity was assessed in HCT116 human colon carcinoma cells by XTT(2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) assay (Scudiero et al,"Evaluation of a soluble tetrazolium/formazan assay for cell growth anddrug sensitivity in culture using human and other tumor cell lines",Cancer Res. 48:4827-4833, 1988). Cells were plated at 4000 cells/well in96 well microtiter plates and 24 hours later drugs were added and serialdiluted. The cells were incubated at 37° C. for 72 hours at which timethe tetrazolium dye, XTT, was added. A dehydrogenase enzyme in livecells reduces the XTT to a form that absorbs light at 450 nm which canbe quantitated spectrophotometrically. The greater the absorbance thegreater the number of live cells. The results are expressed as an IC₅₀which is the drug concentration required to inhibit cell proliferation(i.e. absorbance at 450 nm) to 50% of that of untreated control cells.

Except for compounds 67-2 (Example 118), 66-3 (Example 99), and 48-1(Example 110), all compounds had an IC₅₀ of less than 0.1, indicatingthat they are cytotoxically active. Compounds 67-2 and 66-3 were foundto have an IC₅₀ of substantially more than 0.1 and 48-1 was found tohave an IC₅₀ of at least 0.084.

What I claim is:
 1. A taxane having the formula ##STR145## wherein X₁ is--OX₆, --SX₇, or --NX₈ X₉ ;X₂ is hydrogen, or substituted orunsubstituted alkyl, alkenyl, alkynyl, aryl, or heteroaryl; X₃ and X₄are independently hydrogen, or substituted or unsubstituted alkyl,alkenyl, alkynyl, aryl or heteroaryl; X₅ is --COOX₁₀ ; X₆ is hydrogen,or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, orheteroaryl, or hydroxy protecting group, or a functional group whichincreases the water solubility of the taxane derivative; X₇ issubstituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, orheteroaryl, or sulfhydryl protecting group; X₈ is hydrogen, orsubstituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, orheteroaryl, or heterosubstituted alkyl, alkenyl, alkynyl, aryl orheteroaryl; X₉ is an amino protecting group; X₁₀ is substituted orunsubstituted alkyl, alkenyl or aryl; R₁ is hydroxy, protected hydroxyor together with R₁₄ forms a carbonate; R₂ is hydrogen, hydroxy,--OCOR₃₁, or together with R_(2a) forms an oxo; R_(2a) is hydrogen ortaken together with R₂ forms an oxo; R₄ is hydrogen, or together withR_(4a) forms an oxo, oxirane or methylene; R_(4a) is hydrogen, orsubstituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, orheteroaryl, or cyano, hydroxy, --OCOR₃₀, or together with R₄ forms anoxo, oxirane or methylene; R₅ is hydrogen or together with R_(5a) formsan oxo; R_(5a) is hydrogen, hydroxy, protected hydroxy, acyloxy, ortogether with R₅ forms an oxo; R₆ is hydrogen, or substituted orunsubstituted alkyl, alkenyl, alkynyl, aryl, or heteroaryl, or hydroxy,protected hydroxy or together with R_(6a) forms an oxo; R_(6a) ishydrogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl,or heteroaryl, or hydroxy, protected hydroxy or together with R_(6a)forms an oxo; R₇ is hydrogen or together with R_(7a) forms an oxo;R_(7a) is hydrogen, halogen, protected hydroxy, --OR₂₈, or together withR₇ forms an oxo; R₉ is hydrogen or together with R_(9a) forms an oxo;R_(9a) is hydrogen, hydroxy, protected hydroxy, acyloxy, or togetherwith R₉ forms an oxo; R₁₀ is hydrogen or together with R_(10a) forms anoxo; R_(10a) is hydrogen, --OCOR₂₉, hydroxy, or protected hydroxy, ortogether with R₁₀ forms an oxo; R₁₄ is hydrogen, or substituted orunsubstituted alkyl, alkenyl, alkynyl, aryl, or heteroaryl, or hydroxy,protected hydroxy or together with R₁ forms a carbonate; R_(14a) ishydrogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl,or heteroaryl; R₂₈ is hydrogen, acyl, hydroxy protecting group or afunctional group which increases the solubility of the taxanederivative; and R₂₉, R₃₀, and R₃₁ are independently hydrogen, orsubstituted or unsubstituted alkyl, alkenyl, alkynyl, monocyclic aryl ormonocyclic heteroaryl.
 2. A pharmaceutical composition which containsthe taxane [derivative] of claim 1 and one or more pharmacologicallyacceptable, inert or physiologically active diluents or adjuvants. 3.The taxane of claim 1 wherein X₁₀ is alkenyl or aryl.
 4. The taxane ofclaim 1 wherein X₁₀ is allyl, crotyl, or benzyl.
 5. The taxane of claim1 wherein X₁₀ is alkyl.
 6. The taxane of claim 1 wherein X₁₀ is methyl,ethyl, cyclopropyl, iso- or n-propyl, cyclohexyl, 1,3-diethoxy-2-propyl,2-methoxy-ethyl, amyl, neopentyl, n-butyl, iso-butyl or tert-butyl. 7.The taxane of claim 1 wherein R₁ is hydroxy.
 8. The taxane of claim 1wherein R₂ is benzoyloxy, and R_(2a) is hydrogen.
 9. The taxane of claim1 wherein R_(4a) is acetoxy.
 10. The taxane of claim 1 wherein R. andR_(6a) are hydrogen.
 11. The taxane of claim 1 wherein R₇ is hydrogen,and R_(7a) is hydroxy or protected hydroxy.
 12. The taxane of claim 1wherein R_(9a) together with R₉ forms an oxo.
 13. The taxane of claim 1wherein R₁₀ is hydrogen; and R_(10a) is acetoxy, hydroxy, or protectedhydroxy.
 14. The taxane of claim 1 wherein R₁₄ and R_(14a) are hydrogen.15. The taxane of claim 1 wherein X₁ is --OX₆ ; X₂ is hydrogen or alkyl;X₄ is hydrogen; and X₆ is hydrogen or hydroxy protecting group.
 16. Thetaxane of claim 1 whereinR₁ is hydroxy; R_(2a) is hydrogen, and R₂ is--OCOR₃₁ ; R_(4a) is --OCOR₃₀ ; R₆ and R_(6a) are hydrogen; R₇ ishydrogen, and R_(7a) is hydroxy or protected hydroxy; R_(9a) togetherwith R₉ forms an oxo; R₁₀ is hydrogen, and R_(10a) is --OCOR₂₉, hydroxy,or protected hydroxy; R₁₄ and R_(14a) are hydrogen; R₂₉ and R₃₀ areindependently substituted or unsubstituted alkyl; and R₃₁ is substitutedor unsubstituted monocyclic aryl.
 17. The taxane of claim 15 whereinR₁is hydroxy; R_(2a) is hydrogen, and R₂ is --OCOR₃₁, R_(4a) is --OCOR₃₀ ;R₆ and R_(6a) are hydrogen; R₇ is hydrogen, and R_(7a) is hydroxy orprotected hydroxy; R_(9a) together with R₉ forms an oxo; R₁₀ ishydrogen, and R_(10a) is --OCOR₂₉, hydroxy, or protected hydroxy; R₁₄and R_(14a) are hydrogen; R₂₉ and R₃₀ are independently substituted orunsubstituted alkyl; and R₃₁ is substituted or unsubstituted monocyclicaryl.
 18. The taxane of claim 17 wherein R₂ is benzoyloxy.
 19. Thetaxane of claim 17 wherein R_(4a) and R₂₉ are acetoxy.
 20. The taxane ofclaim 1 wherein R₁ together with R₁₄ forms a carbonate.
 21. The taxaneof claim 1 wherein R₃₁ is hydrogen, or substituted or unsubstitutedalkyl, alkenyl, alkynyl, or monocyclic heteroaryl.
 22. The taxane ofclaim 1 wherein R₃₀ is hydrogen, or substituted or unsubstitutedalkenyl, alkynyl, monocyclic aryl or monocyclic heteroaryl.
 23. Thetaxane of claim 1 wherein R₇ is hydrogen or together with R_(7a) formsan oxo; R_(7a) is hydrogen, halogen, --OR₂₈, or together with R₇ formsan oxo; and R₂₈ is acyl or a functional group which increases thesolubility of the taxane derivative.
 24. The taxane of claim 1 whereinR₉ is hydrogen, and R_(9a) is hydrogen, hydroxy, protected hydroxy, oracyloxy.
 25. The taxane of claim 1 wherein R₁₀ is hydrogen or togetherwith R_(10a) forms an oxo; and R_(10a) is hydrogen or together with R₁₀forms an oxo.
 26. The taxane of claim 1 wherein R₁₄ is substituted orunsubstituted alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy,protected hydroxy or together with R₁ forms a carbonate.
 27. A taxanehaving the formula ##STR146## wherein X₁ is --X₆, --SX₇, or --NX₈ X₉ ;X₂is hydrogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl,aryl, or heteroaryl; X₃ and X₄ are independently hydrogen, orsubstituted or unsubstituted alkyl, alkenyl, alkynyl, aryl orheteroaryl; X₅ is --COOX₁₀ ; X₆ is hydrogen, or substituted orunsubstituted alkyl, alkenyl, alkynyl, aryl, or heteroaryl, or hydroxyprotecting group; X₇ is substituted or unsubstituted alkyl, alkenyl,alkynyl, aryl, or heteroaryl, or sulfhydryl protecting group; X₈ ishydrogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl,or heteroaryl; X₉ is an amino protecting group; X₁₀ is substituted orunsubstituted alkyl, alkenyl or aryl; R₁ is hydroxy, protected hydroxyor together with R₁₄ forms a carbonate; R₂ is hydrogen, hydroxy, or--OCOR₃₁ ; R_(2a) is hydrogen; R₄ is hydrogen, or together with R_(4a)forms an oxo, oxirane or methylene; R_(4a) is hydrogen, or substitutedor unsubstituted alkyl, alkenyl, alkynyl, aryl, or heteroaryl, or cyano,hydroxy, --OCOR₃₀, or together with R₄ forms an oxo, oxirane ormethylene; R₅ is hydrogen or together with R_(5a) forms an OXO; R_(5a)is hydrogen, hydroxy, protected hydroxy, acyloxy, or together with R₅forms an oxo; R₆ and R_(6a) are hydrogen; R₇ is hydrogen; R_(7a) ishydrogen, halogen, protected hydroxy, or --OR₂₈ ; R₉ is hydrogen ortogether with R_(9a) forms an Oxo; R_(9a) is hydrogen, hydroxy,protected hydroxy, acyloxy, or together with R₉ forms an oxo; R₁₀ ishydrogen or together with R_(10a) forms an oxo; R_(10a) is hydrogen,--OCOR₂₉, hydroxy, or protected hydroxy, or together with R₁₀ forms anoxo; R₁₄ is hydrogen, hydroxy, protected hydroxy or together with R₁forms a carbonate; R_(14a) is hydrogen; and R₂₈ is hydrogen, acyl, orhydroxy protecting group; R₂₉, R₃₀ and R₃₁ are independently hydrogen,or substituted or unsubstituted alkyl, alkenyl, alkynyl, monocyclic arylor monocyclic heteroaryl.
 28. The taxane of claim 27 wherein X₁₀ isalkenyl or aryl.
 29. The taxane of claim 27 wherein X₁₀ is allyl,crotyl, or benzyl.
 30. The taxane of claim 27 wherein X₁₀ is alkyl. 31.The taxane of claim 27 wherein X₁₀ is methyl, ethyl, cyclopropyl, iso-or n-propyl, cyclohexyl, 1,3-diethoxy-2-propyl, 2-methoxy-ethyl, amyl,neopentyl, n-butyl, iso-butyl or tert-butyl.
 32. The taxane of claim 27wherein X₁ is --OX₆ ; X₂ is hydrogen or alkyl; X₄ is hydrogen; and X₆ ishydrogen or hydroxy protecting group.
 33. The taxane of claim 1wherein:R₄ is hydrogen, or together with R,, forms an oxo, oxirane ormethylene; R₄ is hydrogen, hydroxy, alkyl, or together with R₄ forms anoxo, oxirane or methylene; R₅ is hydrogen; R_(5a) is hydrogen, hydroxy,protected hydroxy or acyloxy; and R₃₀ is as defined in claim
 1. 34. Thetaxane of claim 27 wherein:R₄ is hydrogen, or together with R_(4a) formsan oxo, oxirane or methylene; R₄ is hydrogen, hydroxy, alkyl, ortogether with R₄ forms an oxo, oxirane or methylene; R₅ is hydrogen;R_(5a) is hydrogen, hydroxy, protected hydroxy or acyloxy; and R₃₀ is asdefined in claim 27.